Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis / Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística

Abstract Objective: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. Methods: Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. Results: This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC). Conclusions: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

Resumo Objetivo: A proteína interleucina 8 promove respostas inflamatórias, o que inclui sua atuação nas vias aéreas. A presença de variantes no gene da interleucina 8 causa respostas inflamatórias alteradas e possivelmente respostas variadas ao uso de broncodilatadores inalatórios. Assim, este estudo analisou as variantes da interleucina 8 (rs4073, rs2227306, rs2227307) e sua associação à resposta a broncodilatadores inalatórios em pacientes com fibrose cística. Métodos: Foi feita análise das variantes genéticas da interleucina 8 por restriction fragment length polymorphism da reação em cadeia da polimerase. A associação entre os marcadores da espirometria e a resposta a broncodilatadores inalatórios foi feita pelos testes de Mann-Whitney e Kruskal-Wallis. A análise incluiu todos os pacientes com fibrose cística e posteriormente pacientes com duas mutações no gene cystic fibrosis transmembrane conductance regulator pertencentes às Classes I a II. Resultados: Este estudo incluiu 186 pacientes com fibrose cística. Não houve associação da variante rs2227307 à resposta a broncodilatadores inalatórios. A variante rs2227306 foi associada a FEF50% no grupo dominante e no grupo com duas mutações identificadas no gene cystic fibrosis transmembrane conductance regulator. A variante rs4073 foi associada a marcadores da espirometria em quatro modelos genéticos: codominante (FEF25-75% e FEF75%), dominante (VEF1, FEF50%, FEF75% e FEF25-75%), recessivo (FEF75% e FEF25-75%) e overdominante (VEF1/CVF). Conclusões: Este estudo destaca, principalmente, a importância da variante rs4073 do gene da interleucina 8, na resposta a broncodilatadores inalatórios, concomitantemente ao genótipo das mutações no gene cystic fibrosis transmembrane conductance regulator.

Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis.

OBJECTIVE: Interleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. METHODS: Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann-Whitney and Kruskal-Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. RESULTS: This study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25-75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25-75%), recessive (FEF75% and FEF25-75%), and over-dominant (FEV1/FVC). CONCLUSIONS: This study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene.

IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability.

The severity of cystic fibrosis (CF) is associated with classes of mutations in the CFTR gene (cystic fibrosis transmembrane regulator), physical environment and modifier genes interaction. The IL8 gene (interleukin 8), according to its respective polymorphisms, influences inflammatory responses. This study analyzed IL8 gene polymorphisms (rs4073, rs2227306 and rs2227307), by means of PCR/RFLP, and their association with pulmonary function markers and clinical severity scores in 186 patients with CF, considering the CFTR genotype. There was an association between rs2227307 and precocity of the disease. The severity of lung disease was associated with the following markers: transcutaneous arterial hemoglobin oxygen saturation (SaO2) (regardless of CFTR genotype, for the polymorphisms rs4073, rs2227306 and rs2227307); mucoid Pseudomonas aeruginosa (regardless of CFTR genotype, for the polymorphisms rs2227306 and rs2227307). Pulmonary function markers (SaO2 and spirometric variables) and clinical severity scores were also associated with IL8 gene polymorphisms. This study identified the IL8 gene, represented by rs4073 and rs2227306 polymorphisms, and particularly the rs2227307 polymorphism, as potentiating factors for the degree of variability in the severity of CF, especially in pulmonary clinical manifestation correlated with increased morbidity and mortality.

Asma, competência social e transtornos comportamentais em crianças e adolescentes / Asthma, social skills and behavioral disorders in children and adolescents

O objetivo deste estudo foi avaliar competência social e transtornos comportamentais em crianças com asma. Participaram 62 crianças (sete a 16 anos) com asma moderada e grave e um grupo controle, cujos pais responderam à versão brasileira do Child Behavior Checklist. Houve associação entre asma e déficit na competência social global (p=0,000), na competência social associada a atividades (p=0,001) e associada à escola (p=0,010). A gravidade da asma não se mostrou associada à competência social. Houve associação entre transtornos comportamentais e asma, principalmente transtornos internalizantes, como ansiedade e depressão, que não se mostraram associados ao gênero, idade e tipo de asma. Concluiu-se que crianças com asma apresentaram mais alterações na competência social global e competência social relacionada a atividades e escola, quando comparadas ao grupo controle. Apresentaram, ainda, mais transtornos globais e internalizantes, que podem prejudicar seu desenvolvimento, qualidade de vida e o manejo adequado da doença.(AU)

The aim of this study was to assess social skills and behavioral disorders in children with asthma. Participants included 62 children/adolescents (between 7 and 16 years of age) with moderate and severe asthma and a control group whose parents completed the Brazilian version of the Child Behavior Checklist. Results: There is evidence of an association between asthma and deficiencies in overall social skills related to activities (p=0.001) and school (p=0.01). The severity of the asthma has no clear link to social skills. There is evidence of an association between behavioral disorders and asthma, especially internalizing disorders, such as anxiety and depression, irrespective of sex, age and severity of asthma. Children/adolescents with asthma had more problems with general social skills and skills associated with activities and school, when compared to the control group. They also had more general and internalizing disorders, which may impair their progress, quality of life and the satisfactory management of the illness.(AU)

Asma, competência social e transtornos comportamentais em crianças e adolescentes / Asthma, social skills and behavioral disorders in children and adolescents

O objetivo deste estudo foi avaliar competência social e transtornos comportamentais em crianças com asma. Participaram 62 crianças (sete a 16 anos) com asma moderada e grave e um grupo controle, cujos pais responderam à versão brasileira do Child Behavior Checklist. Houve associação entre asma e déficit na competência social global (p=0,000), na competência social associada a atividades (p=0,001) e associada à escola (p=0,010). A gravidade da asma não se mostrou associada à competência social. Houve associação entre transtornos comportamentais e asma, principalmente transtornos internalizantes, como ansiedade e depressão, que não se mostraram associados ao gênero, idade e tipo de asma. Concluiu-se que crianças com asma apresentaram mais alterações na competência social global e competência social relacionada a atividades e escola, quando comparadas ao grupo controle. Apresentaram, ainda, mais transtornos globais e internalizantes, que podem prejudicar seu desenvolvimento, qualidade de vida e o manejo adequado da doença.

The aim of this study was to assess social skills and behavioral disorders in children with asthma. Participants included 62 children/adolescents (between 7 and 16 years of age) with moderate and severe asthma and a control group whose parents completed the Brazilian version of the Child Behavior Checklist. Results: There is evidence of an association between asthma and deficiencies in overall social skills related to activities (p=0.001) and school (p=0.01). The severity of the asthma has no clear link to social skills. There is evidence of an association between behavioral disorders and asthma, especially internalizing disorders, such as anxiety and depression, irrespective of sex, age and severity of asthma. Children/adolescents with asthma had more problems with general social skills and skills associated with activities and school, when compared to the control group. They also had more general and internalizing disorders, which may impair their progress, quality of life and the satisfactory management of the illness.

Infecções pelo Vírus Sincicial Respiratório em crianças / Respiratory Syncytial Virus Infections in children

As infecções respiratórias agudas são importante causa de morbimortalidade em pediatria em todo o mundo, particularmente nos países em desenvolvimento. As infecções respiratórias são responsáveis por mais de 25 de todo o atendimento médico pediátrico ambulatorial e hospitalar e, em torno de 90 dessas infecções são relacionadas com agentes virais. O vírus sincicial respiratório (VSR)possui distribuição mundial e constitui a causa mais comum de pneumonia viral em crianças com menos de 5 anos de idade. A bronquiolite ou a pneumonia grave têm probabilidade elevada de ocorrência em lactantes com cerca de 6 semanas de idade, com incidência máxima aos 2 meses. A infecção pelo VSR em lactantes e crianças de mais idade resulta em infecção das vias respiratórias menos agressiva do que aquela observada em lactentes com menos de 6 meses de idade. No hemisfério setentrional, os surtos de infecção pelo VSR tendem a terseu pico no inverno. Nas regiões tropicais, as epidemias pelo VSR iniciamîse no outono e vão até a primavera. A reinfecção é freqüente, porém os sintomas resultantes são mais leves, envolvendo as vias aéreas superiores. Nesta revisão são abordados aspectos importantes das infecções respiratórias por VSR relativos às características do VSR, imunidade, transmissão, epidemiologia, clínica e patologia, prevenção, tratamento, e mortalidade

Osteopetrose: relato de um caso / Osteopetrosis: case report

Relata-se um caso clínico de osteopetrose congênita grave, em uma criança do sexo feminino, com mabisfetaçäo precoce, cuja sintomatologia se fez evidente desde os primeiros meses de vida, sendo o diagnóstico baseado em achados clínicos, laboratoriais e , particularmente, radiológico.