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.

Association of autophagy related gene polymorphisms with neutrophilic airway inflammation in adult asthma

BACKGROUND/AIMS: Role of autophagy in neutrophil function and the association of autophagy and autophagy related (ATG) gene polymorphisms with asthma susceptibility were suggested. In this study, we investigated the genetic association of ATG5 and ATG7 polymorphisms with asthma risk, severity and neutrophilic airway inflammation. METHODS: We recruited 408 asthma patients and 201 healthy controls. Sputum neutrophil counts were determined by H&E staining. Serum interleukin 8 (IL-8) levels were measured by enzyme-linked immunosorbent assay (ELISA). Genetic polymorphisms of ATG5 (-769T>C, -335G>A, and 8830C>T) and ATG7 (-100A>G and 25108G>C) were genotyped. The functional activities of ATG5 -769T>C and -335G>A variants were investigated by luciferase reporter assays. RESULTS: No associations of ATG5 and ATG7 polymorphisms with asthma susceptibility and severity were found. ATG5 -769T>C and -335G>A were in complete linkage disequilibrium. In the asthma group, GA/AA genotypes at ATG5 -335G>A were associated with higher neutrophil counts in sputum (p T associated with lower FEV1% predicted value (p G and 25108G>C were significantly associated with high serum levels of IL-8 (p < 0.05 for both variants). CONCLUSIONS: Genetic polymorphisms of ATG5 and ATG7 could contribute to neutrophilic airway inflammation in the pathogenesis of adult asthma.

A study on human leukocyte antigen class I molecules in paediatric bronchial asthma.

Childhood asthma, often associated with atopy, is more common in boys and may persist throughout life in 50% of cases. This case-control study was carried out to examine if any association of paediatric bronchial asthma with human leukocyte antigen (HLA) class I antigens. Thirty-six children with bronchial asthma diagnosed on basis of Global Initiative for Asthma (GINA) criteria and an equal number of healthy controls without history of bronchial asthma were studied. Low resolution HLA- ABC typing was performed by sequence specific primers (SSP) and the frequency of HLA–ABC antigens in the two groups was compared. Total serum immunoglobulin E (IgE) estimation was done as a marker of atopy by ELISA. The study included 24 boys and 12 girls aged 13 months to 11 yrs, of which 16 (44%) had positive family history. Serum IgE levels were elevated in 20 (55%) of the cases and 33% of controls with peak values of 4877 and 627 IU/ml, respectively. No statistically significant correlation was observed between childhood asthma and HLA class I antigens, however, a statistically significant correlation was observed between serum IgE levels and asthma, which was elevated in cases, as compared to normal population. Serum IgE levels did not show a linear trend, in that a direct correlation with the severity of disease was not observed.

Hematological screening of heavy metals among patients of asthma using medicinal herbs in Karachi, Pakistan

Prevalence and concentration of some toxic [Pb, Cd, and As] and essential metals [Zn, Cu, Cr, Ni, and Co] were determined in the blood samples collected from asthmatic patients in Karachi, Pakistan using atomic absorption spectrophotometer. All selected patients were habitual of taking crude drugs and home remedy as self medication to treat and prevent asthma. We detected large proportion of the patients with detectable levels of heavy metals. The percentage prevalence of Pb, Cr, Ni, and Co, were found 100% while that of As and Cd were 55% and 60% respectively. Atomic absorption spectroscopic data showed the presence of metals in the analyzed samples in the range of 0.00-37.08 microg/dl for As, 8.1-41.4 microg/dl for Pb, 0.0-9.6 microg/l for Cd, 2.0-55.6 microg/l for Cr, 20.0-85.9 microg/l for Ni, and 0.15-3.6 microg/l for Co. The study will be helpful in creating awareness regarding the use of quality herbal medicines in asthma. It is suggested that along with avoidance of other risk factors, reliance on the use of quality traditional medicines free from heavy metal contamination is very essential especially incase of bronco asthmatic conditions

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.

Comparison of Specific IgE Antibodies to Wheat Component Allergens in Two Phenotypes of Wheat Allergy

Specific IgE to gliadin was proposed as a marker for wheat dependent exercise induced anaphylaxis, while Tri a 14 was found to induce IgE response in baker's asthma. We evaluated whether these components could be used for discriminating phenotypes of wheat allergy. Twenty-nine patients who were wheat-induced anaphylaxis and/or urticaria (n=21, group I) and baker's asthma (n=8, group II) were enrolled. The prevalence of serum specific IgE to Tri a 14 was higher in group II (25%) than in group I (4.8%), while the serum specific IgE to gliadin was significantly higher in group I (70%) than in group II (12.5%). The cutoff value for predicting the baker's asthma using the ratio of serum specific IgE to Tri a 14 to gliadin was 742.8 optical densityx1,000/(kU/L) with high sensitivity and specificity. These findings suggest that Tri a 14/gliadin may be a potential marker for predicting baker's asthma.

Role of vitamin D-binding protein in isocyanate-induced occupational asthma

The development of a serological marker for early diagnosis of isocyanate-induced occupational asthma (isocyanate-OA) may improve clinical outcome. Our previous proteomic study found that expression of vitamin D-binding protein (VDBP) was upregulated in the patients with isocyanate-OA. In the present study, we evaluated the clinical relevance of VDBP as a serological marker in screening for isocyanate-OA among exposed workers and its role in the pathogenesis of isocyanate-OA. Three study groups including 61 patients with isocyanate-OA (group I), 180 asymptomatic exposed controls (AECs, group II), 58 unexposed healthy controls (NCs, group III) were enrolled in this study. The baseline serum VDBP level was significantly higher in group I compared with groups II and III. The sensitivity and specificity for predicting the phenotype of isocyanate-OA with VDBP were 69% and 81%, respectively. The group I subjects with high VDBP (> or = 311 microg/ml) had significantly lower PC20 methacholine levels than did subjects with low VDBP. The in vitro studies showed that TDI suppressed the uptake of VDBP into RLE-6TN cells, which was mediated by the downregulation of megalin, an endocytic receptor of the 25-hydroxycholecalciferol-VDBP complex. Furthermore, toluene diisocyanate (TDI) increased VEGF production and secretion from this epithelial cells by suppression of 1,25-dihydroxycholecalciferol [1,25(OH)2D3] production. The findings of this study suggest that the serum VDBP level may be used as a serological marker for the detection of isocyanate-OA among workers exposed to isocyanate. The TDI-induced VEGF production/secretion was reversed by 1,25(OH)2D3 treatment, which may provide a potential therapeutic strategy for patients with isocyanate-OA.

[ comparative study of serum zinc level between asthmatic and control group]

During the past decade Asthma have been increased worldwide. Free radicals have been proposed to be responsible or the pathogenesis of many diseases because of their harmful effects on the cells and tissues. There are some defense mechanisms in the organism to avoid the harmful effects of free radicals. The most important antioxidants are glutathione peroxidase and superoxide dismutase. Glutathione peroxidase has selenium and superoxide dismutase system has zinc in their structures which diminish the harmful effects of oxygen free radicals. This research was done to analyze the relation between serum zinc concentrations as antioxidant in children asthma. This was a case study. We made comparison between 80 asthmatic patients. Who attended the pediatric allergy outpatients clinics and 80 control group children who attended the pediatric outpatient clinic for the complaints of non specific non-chronic disorders [acute upper respiratory system infection, urinary tract infection e.t.c] without any of history of atopy. None of the patients in the study used systemic or inhaled steroids and nonsterioidal anti inflammatory for the last 2 weeks. The serum zinc was measured with manual calorimetric method and then the results were compared. In this study the overage age in case group was [6.07 +/- 2.07 yrs] and in control group was [5.25 +/- 3.44 yrs]. Therefore, no significant difference was detected. In view of gender both groups were totally identical. Mean serum zinc in patients was 93.93 +/- 25.58 mg/dl and in controls was 97.18 +/- 23.59 mg/dl; With no statistical difference [P>0.05]. It was not approved that serum zinc concentrations were lower in the asthmatic patients than normal individuals

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.

Complement components (C3, C4) as Inflammatory markers in asthma.

Objective. To assess the serum levels of complement factors C3 and C4 in Egyptian asthmatic children. Methods. This case-controlled study comprised of 60 Egyptian children with the diagnosis of bronchial asthma (not in acute attack) and 60 age-and sex-matched healthy controls. All candidates were subjected to a thorough clinical study, complete blood counts, absolute eosinophil count and serum complements (C3, C4). Results. Serum C3 was significantly higher in asthmatics when compared to controls (140.60 ± 38.80 mg/dl vs 107.70 ± 45.00 mg/dl respectively, (p = 0.01). However, differences in serum C4 levels were not significant (41.30±48.80 mg/dl vs 44.60 ± 39.70 mg/dl respectively, p = 0.69). There was a significant positive correlation between severity of asthma and serum C3 (p=0.02) but not with serum C4. Conclusions. Serum levels of C3 - but not C4 - are elevated in children with stable asthma, with a positive correlation between serum C3 and severity of asthma.

[ comparison of serum CRP levels measured by a highly sensitive method in healthy subjects and asthmatic patients]

C- reactive protein [CRP] is a plasma protein which is a marker of inflammation. Recently it has been shown that the increased level of CRP is associated with increased risk of MI, IHD, DM and hypertension. There are plenty of published articles in regard to the role of CRP in the pathogenesis of COPD. Also a potential role for CRP in the pathogenesis of asthma has been proposed. The local inflammation is an established pathology in the asthma however, little is known about role of systemic inflammation. We compared serum levels of highly sensitive CRP between steroid inhaling asthmatic patients and non asthmatic healthy controls. This case-control study, based on standard criteria, included fifty known cases of asthmatic patients who met the inclusion criteria and fifty non asthmatic subjects. Serum levels of CRP were measured and compared with each other in both groups by ELISA method. All asthmatics were at the same stage of treatment. The mean age of the asthmatic patients was 46.9 +/- 9.8 years and that of control group was 44 +/- 14.35 years. Durations of pulmonary symptoms were <3 years in 20%, 3-5 years in 36%, 6-12 years in 24% and >13years in 20% of the patients. HS-CRP levels were significantly higher in asthmatic patients than in control patients [34.79 mg/dl versus 12.8 mg/dl respectively] [P=0.001]. HS-CRP levels had no significant relation with age, gender and duration of asthma. In asthma inflammation is not limited to airways and like COPD, evidence of systemic inflammation such as increased CRP can be detected

Eosinophilic cationic protein: is it useful in assessing control of childhood asthma?

This study evaluated peripheral eosinophil and serum eosinophilic cationic protein [s-ECP] levels as markers of asthma control. A total of 38 children with asthma [16 controlled and 22 partially controlled] were compared with 16 age- and sex-matched healthy children. Total asthma cases had higher eosinophil counts and s-ECP levels than healthy children and partially controlled asthmatics had significantly higher levels of both markers than controlled asthmatics. Controlled asthma cases showed non-significant changes in both parameters versus healthy children. A negative correlation was noted between degree of asthma control and both eosinophil counts and s-ECP levels [r = -0.60 and -0.75 respectively]. s-ECP as well as peripheral eosinophil count may be helpful in the assessment of asthma control

A study of high-sensitivity c-reactive protein in bronchial asthma.

Background. Relevance of C-reactive protein an acute phase reactant and a sensitive marker of low-grade systemic inflammation in bronchial asthma has not been fully studied. Objective. To evaluate the significance of high-sensitivity C-reactive protein (hs-CRP) in atopic and non-atopic asthma using an ultra sensitive assay. Methods. The levels of hs-CRP of 200 patients with bronchial asthma and 50 non-asthmatic control subjects were measured using a Latex enhanced immunoturbidimetric test. Spirometry with reversibility study, serum immunoglobulin-E (IgE) measurement and skin test for allergy was done in all the patients. Results. There was a significant increase in hs-CRP levels with age in atopic asthmatics but no such association was observed in the non-atopic asthmatics and control subjects. The hs-CRP levels were not influenced by sex in any group. Smokers in all the three groups had a significantly higher hs-CRP levels as compared to non-smokers. Patients with asthma had higher hs-CRP values as compared to controls. Patients with non-allergic asthma had higher mean hs-CRP as compared to atopic asthmatics and control subjects. Conclusions. The study suggests that there exists a certain degree of low-grade systemic inflammation in addition to the local bronchial inflammation in non-atopic asthmatics. Hence, hs-CRP may be used as a surrogate marker for the airway inflammation in non-atopic asthma patients.

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...