Adyléia Aparecida Dalbo Contrera Toro

Association of TGF-beta1, CD14, IL-4, IL-4R and ADAM33 gene polymorphisms with asthma severity in children and adolescents

OBJECTIVE To verify the association of transforming growth factor-beta1(TGF-beta1) (C-509T and T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) and ADAM33 (S_2) gene polymorphisms with asthma severity in a sample of patients with mild, moderate and severe persistent atopic asthma. METHODS A clinical, laboratory, prospective study was performed in patients with persistent atopic asthma, compared to a control group at Hospital Universitário da Universidade Estadual de Campinas between 2006 and 2007. Analysis of the TGF-beta1 T869C gene polymorphism was performed using the technique polymerase chain reaction (PCR) + amplification refractory mutation system (ARMS). TGF-beta1 C-509T, CD14 C-159T, IL-4 C-590T, IL-4Ra ILe50Val, and ADAM33 S2 gene polymorphisms were detected by PCR and restriction enzyme. RESULTS This study included 88 patients with persistent atopic asthma (27 mild, 23 moderate and 38 severe) and 202 healthy blood donors. As to T869C polymorphism (TGF-beta1), there was an association between the CC genotype and patients with severe asthma. There was no association in polymorphisms C-509T (TGF-beta1), C-590T (IL-4) and S_2 (ADAM33). When distribution of C-159T polymorphism genotype frequency (CD14) in severe asthma was compared with the control group, there was a significant result with the TT genotype. There was significant association of the Val/Val genotype (IL-4R) with mild asthma. CONCLUSION Our results indicate that T869C (TGF-beta1), C-159T (CD14) and Val/Val (IL-4R) polymorphisms might be involved in modulation of asthma severity.

Associação dos polimorfismos dos genes TGF-beta1, CD14, IL-4, IL-4R e ADAM33 com a gravidade da asma em crianças e adolescentes

OBJETIVO: Verificar, em uma amostra de pacientes com asma atopica persistente leve, moderada e grave, a associacao entre os polimorfismos dos genes fator de crescimento transformante-b1 (TGF-b1) (C-509T e T869C), CD14 (C-159T), IL-4 (C-590T), IL-4R (ILe50Val) e ADAM33 (S_2) com a gravidade da asma. METODOS: Realizou-se um estudo clinico laboratorial prospectivo em pacientes com asma atopica persistente, comparados a um grupo controle no Hospital Universitario da Universidade Estadual de Campinas nos anos de 2006 e 2007. A analise do polimorfismo T869C do gene TGF-b1 foi realizada pela tecnica de reacao em cadeia da polimerase (PCR) + sistema de amplificacao refrataria de mutacao (ARMS). Os outros polimorfismos, C-509T do gene TGF-b1, C-159T do gene CD14, C-590T da IL-4, ILe50Val da IL-4Ra e S2 do gene ADAM33, foram detectados por PCR e enzima de restricao. RESULTADOS: Foram incluidos 88 pacientes com asma atopica persistente (27 leves, 23 moderados e 38 graves) e 202 individuos saudaveis, doadores de sangue. Em relacao ao polimorfismo T869C (TGF-b1), observou-se uma associacao entre o genotipo CC e os pacientes com asma grave. Nenhuma associacao foi encontrada com os polimorfismos C-509T (TGF-b1), C-590T (IL4) e S_2 (ADAM33). Quando se comparou a distribuicao da frequencia genotipica do polimorfismo C-159T (CD14) na asma grave com o grupo controle, foi observado um resultado significativo com o genotipo TT. Houve associacao significativa do genotipo Val/Val (IL-4R) com a asma leve. CONCLUSAO: Nossos resultados indicam que os polimorfismos T869C (TGF-b1), C-159T (CD14) e Val/Val (IL-4R) podem estar envolvidos na modulacao da gravidade da asma.

Effects of swimming on spirometric parameters and bronchial hyperresponsiveness in children and adolescents with moderate persistent atopic asthma

OBJECTIVE To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). METHODS A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clínicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test--provocative concentration of methacholine causing a 20% fall in FEV1 (PC₂₀)--before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. RESULTS Significant increases in PC₂₀ (pre-training, 0.31±0.25; post-training, 0.63±0.78; p = 0.008), MIP (pre-training, 67.08±17.13 cm H₂O; post-training 79.46±18.66; p < 0.001), and MEP (pre-training, 71.69±20.01 cm H₂O; post-training, 78.92±21.45 cm H₂O; p < 0.001) were found in the swimming group. CONCLUSION Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC₂₀ values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall.

Avaliação espirométrica e da hiper-responsividade brônquica de crianças e adolescentes com asma atópica persistente moderada submetidos a natação

OBJECTIVE: To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). METHODS: A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clinicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test - provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) - before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. RESULTS: Significant increases in PC20 (pre-training, 0.31±0.25; post-training, 0.63±0.78; p = 0.008), MIP (pre-training, 67.08±17.13 cm H2O; post-training 79.46±18.66; p < 0.001), and MEP (pre-training, 71.69±20.01 cm H2O; post-training, 78.92±21.45 cm H2O; p < 0.001) were found in the swimming group. CONCLUSION: Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC20 values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall.

Obesidade e asma: associação ou coincidência?

OBJECTIVE: Asthma and obesity are among the major causes of morbidity in childhood and adolescence. Early obesity increases the chances of chronic degenerative diseases in adults. Although the concomitance or both clinical situations are being demonstrated in various studies, the intrinsic mechanisms of this association are still very little known. Therefore, the objective of this article was to review the main studies on the association of obesity and asthma and check if there is a cause-effect relation between them. SOURCES: Systematic review based on indexed data bases MEDLINE (PubMed) and SciELO. Original articles (cross-sectional, case-control, and prospective studies) and meta-analysis published in the period that ranges from January 1998 to January 2008 were reviewed. Studies published in English, Spanish, and Portuguese were researched. SUMMARY OF THE FINDINGS: Although there are various studies on growing prevalence of asthma and obesity, few of them establish cause-effect relations between them. Physiopathological mechanisms and factors involved in this process are still little known. CONCLUSION: Methodological rigor in future studies must seek for answers to better understand if there is association between asthma and obesity or if the relationship between both diseases is a coincidence.

Obesity and asthma: association or coincidence?

OBJECTIVE Asthma and obesity are among the major causes of morbidity in childhood and adolescence. Early obesity increases the chances of chronic degenerative diseases in adults. Although the concomitance or both clinical situations are being demonstrated in various studies, the intrinsic mechanisms of this association are still very little known. Therefore, the objective of this article was to review the main studies on the association of obesity and asthma and check if there is a cause-effect relation between them. SOURCES Systematic review based on indexed data bases MEDLINE (PubMed) and SciELO. Original articles (cross-sectional, case-control, and prospective studies) and meta-analysis published in the period that ranges from January 1998 to January 2008 were reviewed. Studies published in English, Spanish, and Portuguese were researched. SUMMARY OF THE FINDINGS Although there are various studies on growing prevalence of asthma and obesity, few of them establish cause-effect relations between them. Physiopathological mechanisms and factors involved in this process are still little known. CONCLUSION Methodological rigor in future studies must seek for answers to better understand if there is association between asthma and obesity or if the relationship between both diseases is a coincidence.

Antileukotrienes in the treatment of asthma and allergic rhinitis

OBJECTIVES To compare leukotriene antagonists (LTA) to other groups of drugs used in asthma and allergic rhinitis treatment. SOURCES MEDLINE, LILACS and Cochrane Library. KEYWORDS leukotrienes, antileukotrienes, asthma treatment, allergic rhinitis treatment, asthma and allergic rhinitis. An attempt was made to group the main studies and reviews about this topic. SUMMARY OF THE FINDINGS LTA are more efficient than placebo and enhance the effects of inhaled corticosteroids. The association of inhaled corticosteroids with long-acting Beta2 agonists is more efficient than the association of inhaled corticosteroids + LTA. Although use of LTA in acute asthma attacks and allergic rhinitis seems reasonable, more studies are needed to confirm this benefit. LTA reduce hospitalization time and the number of wheezing attacks in infants with acute viral bronchiolitis caused by respiratory syncytial virus, as well as recurrent wheezing after acute viral bronchiolitis. LTA are less efficient than intranasal corticosteroids for allergic rhinitis management. LTA are efficient in exercise-induced asthma, although they are not the first-line treatment. CONCLUSION Controlled and randomized studies show that inhaled corticosteroids are the drugs of choice to treat persistent asthma and allergic rhinitis. There is not enough evidence to recommend the use of LTA as first-line drug (monotherapy) in children with asthma (level I). For children who cannot use inhaled corticosteroids, LTA may be a good alternative (level II).

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.

Risk factors for gastroesophageal reflux disease in very low birth weight infants with bronchopulmonary dysplasia

OBJECTIVE To assess risk factors for gastroesophageal reflux disease (GERD) in very low birth weight infants with bronchopulmonary dysplasia. METHODS A case-control study was carried out in 23 cases and 23 control subjects with bronchopulmonary dysplasia submitted to 24-hour esophageal pH monitoring between January 2001 and October 2005. Cases and controls were compared for gestational age, birth weight, gender, use of antenatal steroids, duration of assisted ventilation, duration of oxygen therapy, length of gastric tube use, administration of xanthines, postconceptual age, and weight at esophageal pH monitoring. Multiple logistic regression analysis was used to establish the odds ratio (OR) with a 95% confidence interval (95%CI). RESULTS None of the groups (with and without GERD) showed statistically significant differences in terms of demographic variables and postnatal outcome, use of antenatal and postnatal corticosteroids, or in terms of caffeine use and duration of mechanical ventilation and oxygen therapy. However, feeding intolerance (OR = 6.55; 95%CI 1.05-40.8) and length of gastric tube use (OR = 1.67; 95%CI 1.11-2.51) turned out to be risk factors for GERD. Postconceptual age at the time of pH monitoring (OR = 0.02; 95%CI < 0.001-0.38) was regarded as a protective factor against GERD. CONCLUSION The data obtained allow inferring that prolonged gastric tube use and feeding intolerance increase the risk for GERD. On the other hand, older postconceptual age at the time of pH monitoring reduces the risk for GERD in preterm infants with bronchopulmonary dysplasia weighing less than 1,500 g.

Desempenho funcional de pacientes com fibrose cística e indivíduos saudáveis no teste de caminhada de seis minutos

OBJECTIVE To compare patients with cystic fibrosis and healthy individuals in terms of their functional performance on the six-minute walk test (6MWT). METHODS A prospective, cross-sectional study involving healthy individuals and patients with cystic fibrosis treated at a referral university hospital in the city of Campinas, Brazil. The 6MWT was administered in accordance with the American Thoracic Society guidelines, and it was repeated after a 30-min rest period. For all of the participants, RR, HR, SpO2, and Borg scale scores were obtained. For the cystic fibrosis patients, nutritional status and spirometric values were determined. Patients with pulmonary exacerbation were excluded. Spearmans correlation coefficient and repeated measures ANOVA were used. RESULTS The cystic fibrosis group comprised 55 patients, and the control group comprised 185 healthy individuals. The mean ages were 12.2 ± 4.3 and 11.3 ± 4.3 years, respectively. The six-minute walk distance (6MWD) was significantly shorter in the cystic fibrosis group than in the control group for both tests (547.2 ± 80.6 m vs. 610.3 ± 53.4 m for the first and 552.2 ± 82.1 m vs. 616.2 ± 58.0 m for the second; p < 0.0001 for both). The 6MWD correlated with age, weight, and height only in the cystic fibrosis group. During the tests, SpO2 remained stable, whereas HR and RR increased. CONCLUSIONS In our sample, functional performance on the 6MWT was poorer among the cystic fibrosis patients than among the healthy controls in the same age bracket, and we found immediate repetition of the test to be unadvisable.OBJECTIVE: To compare patients with cystic fibrosis and healthy individuals in terms of their functional performance on the six-minute walk test (6MWT). METHODS: A prospective, cross-sectional study involving healthy individuals and patients with cystic fibrosis treated at a referral university hospital in the city of Campinas, Brazil. The 6MWT was administered in accordance with the American Thoracic Society guidelines, and it was repeated after a 30-min rest period. For all of the participants, RR, HR, SpO2, and Borg scale scores were obtained. For the cystic fibrosis patients, nutritional status and spirometric values were determined. Patients with pulmonary exacerbation were excluded. Spearmans correlation coefficient and repeated measures ANOVA were used. RESULTS: The cystic fibrosis group comprised 55 patients, and the control group comprised 185 healthy individuals. The mean ages were 12.2 ± 4.3 and 11.3 ± 4.3 years, respectively. The six-minute walk distance (6MWD) was significantly shorter in the cystic fibrosis group than in the control group for both tests (547.2 ± 80.6 m vs. 610.3 ± 53.4 m for the first and 552.2 ± 82.1 m vs. 616.2 ± 58.0 m for the second; p < 0.0001 for both). The 6MWD correlated with age, weight, and height only in the cystic fibrosis group. During the tests, SpO2 remained stable, whereas HR and RR increased. CONCLUSIONS: In our sample, functional performance on the 6MWT was poorer among the cystic fibrosis patients than among the healthy controls in the same age bracket, and we found immediate repetition of the test to be unadvisable.