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.

RELATIONS BETWEEN ASTHMA AND OBESITY: AN ANALYSIS OF MULTIPLE FACTORS.

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.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children / Aptidão e atividade física, perfil metabólico, adipocinas e função endotelial em crianças

Abstract Objectives: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Method: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). Results: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p < 0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p < 0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p < 0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho = −0.41; p = 0.01), and this association remained after adjusting for body mass index z-score (rho = 0.28; p = 0.03). Conclusion: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Resumo: Objetivos: A prevalência da obesidade está aumentando. O objetivo deste estudo foi investigar se há disfunção endotelial nas crianças com peso normal ou excesso de peso e se o perfil metabólico, as adipocinas e a disfunção endotelial seriam mais fortemente associados à aptidão física ou aos níveis de atividade física. Método: Estudo transversal que envolve crianças de 5-12 anos. A avaliação incluiu pletismografia de oclusão venosa, níveis séricos de adiponectina, leptina, insulina e lipidograma, escore de atividade física (questionário PAQ-C) e avaliação da aptidão física (teste Yo-yo). Resultados: Um total de 62 crianças participou deste estudo. Com base no índice de massa corporal, 27 eram eutróficos, 10 estavam acima do peso e 25 estavam obesos. Os níveis de triglicerídeos, colesterol LDL, HOMA-RI e leptina estavam mais elevados nas crianças obesas e com excesso de peso que o grupo de eutróficos (p < 0,01). Os níveis de colesterol HDL e adiponectina estavam mais elevados no grupo de eutróficos em comparação ao grupo de obesos e com excesso de peso (p < 0,01). A vasodilatação mediada pelo fluxo após hiperemia foi maior no grupo de eutróficos em comparação aos indivíduos obesos e com excesso de peso (p < 0,05). Não houve nenhuma diferença nos níveis de atividade física entre os grupos medidos pelo PAQ-C. O teste de ida e volta foi significativamente associado ao colesterol HDL (ró = −0,41; p = 0,01) e essa associação continuou após ajustar o escore z do índice de massa corporal (ró = 0,28; p = 0,03). Conclusão: Este estudo mostrou que a disfunção endotelial já está presente nas crianças obesas, sugeriu uma predisposição à doença aterosclerótica. Além disso, os níveis de colesterol HDL foram correlacionados à aptidão física, independentemente do índice de massa corporal.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

OBJECTIVES: The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. METHOD: Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). RESULTS: A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p<0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p<0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p<0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). CONCLUSION: This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations.

Abstract. OBJECTIVE: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. MATERIALS AND METHODS: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. RESULTS: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. CONCLUSION: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

OBJETIVO: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. MATERIAIS E MÉTODOS: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. RESULTADOS: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. CONCLUSÃO: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

Ultrasound as a method to evaluate the distribution of abdominal fat in obese prepubertal children and the relationship between abdominal fat and metabolic alterations / A ultrassonografia como método de avaliação da distribuição da gordura abdominal em crianças pré-púberes obesas e sua relação com alterações metabólicas

Abstract Objective: To evaluate, using ultrasound, the distribution of abdominal fat in obese prepubertal children, as well as its possible correlation with metabolic changes due to obesity. Materials and Methods: This was a cross-sectional study of prepubescent children: 77 obese children (33 girls and 44 boys), with a mean age of 7.31 years; and 31 normal-weight children (17 girls and 14 boys), with a mean age of 7.32 years. In all of the children, abdominal wall thickness (AWT) and abdominal fat thickness (AFT) were measured by ultrasound. For the evaluation of the associated metabolic alterations, serum levels of glycemia, HDL cholesterol, triglycerides, and insulin were determined. Results: The obese children presented with greater abdominal fat, predominantly greater AWT, without a significant gender-related difference in AWT or AFT. The homeostasis model assessment of insulin resistance (HOMA-IR) showed a significant direct correlation with AWT and AFT. Conclusion: In obese prepubertal children, the AWT, as measured by ultrasound, was shown to be more closely related to the HOMA-IR than to the lipid metabolism or glycemia.

Resumo Objetivo: Avaliar, em crianças pré-púberes obesas, a distribuição da gordura no abdome por meio da ultrassonografia e sua possível correlação com as alterações metabólicas decorrentes da obesidade. Materiais e Métodos: Estudo transversal em crianças pré-púberes, sendo 77 obesas (33 meninas e 44 meninos) com média de idade de 7,31 anos e 31 eutróficas (17 meninas e 14 meninos) com média de idade de 7,32 anos. Em todas as crianças foram medidas a espessura da parede abdominal (EPA) e a espessura da gordura intra-abdominal (EIA), pela ultrassonografia. Para a avaliação das alterações metabólicas associadas, foi realizada dosagem sérica de glicemia, HDL-colesterol, triglicerídeos e insulina. Resultados: Observou-se que as crianças obesas apresentaram aumento da gordura abdominal, com predomínio da EPA e sem diferença significativa da EIA e a EPA em relação ao gênero. Foi encontrada associação direta estatisticamente significante entre o índice homeostatic model assessment for insulin resistance (HOMA-IR) e EPA e EIA. Conclusão: A EPA em pré-púberes obesos, medida pela ultrassonografia, demonstrou ter maior relação com o HOMA-IR, determinante de resistência insulínica, em relação ao metabolismo lipídico e à glicemia.

Microcirculation, Adiposity, and Traditional and Emerging Cardiovascular Risk Factors in Prepubertal Children.

PURPOSE: Previous studies have shown that microvascular dysfunction (MD) is associated with a number of cardiovascular risk factors, including obesity. Few studies have assessed microvascular reactivity in children, and in most of these, results were confounded by the effects of puberty. Our aim was to establish whether MD is already present in obese prepubertal children. METHODS: This cross-sectional study included 52 obese, 18 overweight, and 28 eutrophic children, with a mean ± standard deviation age of 7.44 ± 1.22 years. We evaluated cardiovascular risk factors and nutritive microvascular function by using nailfold dynamic videocapillaroscopy and determined functional capillary density (FCD), red blood cell velocity at resting conditions (RBCV) and at peak (RBCVmax), and time to reach peak velocity during the post-occlusive reactive hyperemic response following 1 minute ischemia. RESULTS: On univariate analysis, differences in microvascular reactivity were not observed among the groups. Obese and overweight children had significantly higher scores than eutrophic children for the following parameters: body mass index, waist circumference, waist-to-height ratio, mean arterial pressure, homeostasis model assessment for insulin resistance, levels of insulin, leptin, glucose, triglycerides, total cholesterol, uric acid, and C-reactive protein. Multivariate analysis demonstrated the association between metabolic, anthropometric, and microvascular variables, stratified according to the degree of adiposity and body fat distribution. CONCLUSIONS: Univariate analysis did not show any difference in microvascular reactivity between groups but, by testing these variables by multivariate means, we noticed a common and direct variation between cardiovascular/metabolic risk factors and microvascular reactivity occurring early in life.

Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children.

BACKGROUND: Early exposure to cardiovascular risk factors creates a chronic inflammatory state that could damage the endothelium followed by thickening of the carotid intima-media. OBJECTIVE: To investigate the association of cardiovascular risk factors and thickening of the carotid intima. SUBJECTS/METHODS: Media in prepubertal children. In this cross-sectional study, carotid intima-media thickness (cIMT) and cardiovascular risk factors were assessed in 129 prepubertal children aged from 5 to 10 year. Association was assessed by simple and multivariate logistic regression analyses. RESULTS: In simple logistic regression analyses, body mass index (BMI) z-score, waist circumference, and systolic blood pressure (SBP) were positively associated with increased left, right, and average cIMT, whereas diastolic blood pressure was positively associated only with increased left and average cIMT (p<0.05). In multivariate logistic regression analyses increased left cIMT was positively associated to BMI z-score and SBP, and increased average cIMT was only positively associated to SBP (p<0.05). CONCLUSIONS: BMI z-score and SBP were the strongest risk factors for increased cIMT.

The role of metabolic syndrome components and adipokines in insulin resistance in prepubertal children.

OBJECTIVE: Insulin resistance has a central role in the pathophysiology of cardiovascular atherosclerotic disease. Adipose tissue is of capital importance in view of its production of adipokines. The present study aims to determine the association of metabolic syndrome components, which constitute risk factors for cardiovascular atherosclerotic disease, and leptin and adiponectin with insulin resistance in prepubertal children. METHODS: We conducted a cross-sectional study involving 197 children. Of these, 112 children were obese, 36 were overweight and 49 had normal weight. The association of sex, waist circumference, Acanthosis nigricans, age, BMI Z-score, serum lipids, leptin and adipocytokines with insulin resistance [defined as the homeostatic model assessment for insulin resistance (HOMA-IR) index higher than or equal to 2.5] was investigated using logistic regression. RESULTS: There was positive association of sex (female), age, BMI Z-score, triglycerides and leptin with insulin resistance (p<0.05). CONCLUSION: Among the conventional components of metabolic syndrome, the role of BMI Z-score and triglycerides stands out in insulin resistance of prepubertal children. Sex (female), age and leptin also showed to be of major importance.

Ponto de corte do índice Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) avaliado pela curva Receiver Operating Characteristic (ROC) na detecção de síndrome metabólica em crianças pré-púberes com excesso de peso / Cut-off point for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established from Receiver Operating Characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children

OBJETIVO: Estabelecer, entre os pontos de corte do índice homeostatic model assessment for insulin resistance (HOMA-IR), citados na literatura, o melhor em identificar a síndrome metabólica (SM) em crianças com obesidade e sobrepeso. MÉTODOS: Foram estudadas 140 crianças pré-púberes. A definição de SM foi adaptada da International Diabetes Federation. Para cada ponto de corte de HOMA-IR foram estimados sensibilidade e especificidade, tomandose como desfecho a SM. Uma curva receiver operating characteristic (ROC) foi construída com estes valores. RESULTADOS: O grupo estudado constituiu-se de 106 crianças com obesidade (37 meninas e 69 meninos) e 34 com sobrepeso (19 meninas e 15 meninos), média de idade 6,5 ± 2,3 anos. A acurácia da curva ROC foi 72 por cento, e o melhor ponto de corte foi 2,5, com sensibilidade 61 por cento e especificidade 74 por cento. CONCLUSÃO: O índice HOMA-IR pode ser útil para detectar a SM, e o ponto de corte 2,5 mostrou-se o melhor para crianças pré-púberes com obesidade e sobrepeso.

OBJECTIVE: To establish, among the cut-off values for the homeostatic model assessment for insulin resistance index (HOMA-IR) cited in the literature, the best in identifying metabolic syndrome (MS) in obese and overweight children. METHODS: A total of 106 pre-pubertal children were studied. The definition of MS was adapted from that of the International Diabetes Federation. For each cut-off values for HOMA-IR, it was estimated sensibility and specificity for MS. A receiver operating characteristic (ROC) curve was generated using these values. RESULTS: The study included 106 obese (37 girls and 69 boys) and 34 overweight (19 girls and 15 boys) children aged 6,5 ± 2,3 years. The accuracy of the ROC curve was 72 percent, and the best cut-off value for HOMAIR was 2,5, with sensitivity of 61 percent and specificity of 74 percent. CONCLUSIONS: HOMA-IR may be useful to detect MS and the cut-off 2,5 seems to be the best in obese and overweight pre-pubertal children.

[Cut-off point for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index established from Receiver Operating Characteristic (ROC) curve in the detection of metabolic syndrome in overweight pre-pubertal children]. / Ponto de corte do índice Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) avaliado pela curva Receiver Operating Characteristic (ROC) na detecção de síndrome metabólica em crianças pré-púberes com excesso de peso.

OBJECTIVE: To establish, among the cut-off values for the homeostatic model assessment for insulin resistance index (HOMA-IR) cited in the literature, the best in identifying metabolic syndrome (MS) in obese and overweight children. METHODS: A total of 106 pre-pubertal children were studied. The definition of MS was adapted from that of the International Diabetes Federation. For each cut-off values for HOMA-IR, it was estimated sensibility and specificity for MS. A receiver operating characteristic (ROC) curve was generated using these values. RESULTS: The study included 106 obese (37 girls and 69 boys) and 34 overweight (19 girls and 15 boys) children aged 6,5 +/- 2,3 years. The accuracy of the ROC curve was 72%, and the best cut-off value for HOMAIR was 2,5, with sensitivity of 61% and specificity of 74%. CONCLUSIONS: HOMA-IR may be useful to detect MS and the cut-off 2,5 seems to be the best in obese and overweight pre-pubertal children.

[Primary hyperparathyroidism associated to slipped capital femoral epiphysis in a teenager]. / Hiperparatireoidismo primário associado a epifisiólise de cabeça do fêmur em adolescente.

Primary hyperparathyroidism (PHP) is an uncommon disease in children and adolescents. The association between PHP and slipped capital femoral epiphysis is rare, and so far only four cases have been reported in the literature. Herein, we report a case of PHP due to a parathyroid adenoma, with several painful skeletal deformities and associated with slipped capital femoral epiphysis in an 18-year-old male patient. Laboratory evaluation showed: calcium of 13.6 mg/dL, parathyroid hormone of 1,524 pg/mL and alkaline phosphatase of 3,449 U/L. Deformities were caused by late diagnosis during the growth spurt, and this association is the result of combinations between metabolic and mechanical factors. The patient underwent parathyroidectomy and, in agreement with the literature, since the removal of the adenoma is followed by prompt resolution of the slipped capital femoral epiphysis we decided for a conservative approach. We observed improvement of the pain and normalization of calcium and parathyroid hormone levels.

Hiperparatireoidismo primário associado a epifisiólise de cabeca do fêmur em adolescente / Primary hyperparathyroidism associated to slipped capital femoral epiphysis in a teenager

O hiperparatireoidismo primário (HPP) é uma doenca incomum na infância e na adolescência. A associacão de HPP e epifisiólise de cabeca do fêmur é rara, tendo sido descritos apenas quatro casos na literatura. Relatamos um caso de HPP por adenoma de paratireóide, com dores e inúmeras deformidades ósseas, associado a epifisiólise de cabeca do fêmur em um jovem de 18 anos. A análise laboratorial mostrou cálcio de 13,7mg/dL, paratormônio de 1.524pg/mL e fosfatase alcalina de 3.449U/L. As deformidades foram decorrentes de diagnóstico tardio e possivelmente pelo fato de a doenca ter ocorrido na fase de estirão puberal. A combinacão de vários fatores metabólicos e mecânicos provavelmente contribuiu para esta associacão. O paciente foi submetido à remocão cirúrgica do adenoma, que costuma ser acompanhada por resolucão pronta da epifisiólise. Desta forma, foi optado por conduta expectante quanto à epifisiólise da cabeca do fêmur, em consonância com a literatura. Houve melhora das dores ósseas e normalizacão dos níveis de cálcio e de paratormônio.