RESUMO
BACKGROUND: Atopic dermatitis (AD) and respiratory syncytial virus lower respiratory tract infection (RSV LRTI) are common diseases during early life. Impaired Th1-cell polarizing Toll-like receptor (TLR) responses play an important role in the pathogenesis of both diseases. Neonatal TLR-mediated production of Th1-type cytokines is decreased at birth, but rapidly increases during the first month of life. OBJECTIVE: To determine whether decreased TLR-mediated production of Th1-polarizing cytokines, at the age of 1 month is associated with subsequent AD or RSV LRTI. METHODS: A prospective healthy birth cohort study was performed. Whole blood concentrations of innate immune cells and TLR-mediated cytokine responses were measured at the age of 1 month in 291 neonates. AD was determined by a physician questionnaire at the age of 1 year and RSV LRTI was defined as parent-reported respiratory symptoms and presence of RSV RNA in a nose-throat specimen. RESULTS: Of participating neonates, 45 (15%) developed AD and 41 (14%) developed RSV LRTI. Risks of AD and RSV LRTI were not associated (χ(2) , P = 1.00). AD was associated with decreased concentrations of basophils (7.6 vs. 14.0 × 10(6) /mL, P = 0.002) and plasmacytoid dendritic cells (17.0 vs. 20.5 × 10(6) /mL, P = 0.04), increased concentrations of NK-cells (79.7 vs. 45.1 × 10(6) /mL, P = 0.03), and twofold lower TLR4-mediated IL-10 production (P = 0.001). In contrast, RSV LRTI was associated neither with neonatal concentrations of innate immune cells, nor with TLR-mediated TNF-α, IL-12p70, IL-10 or IFN-α production. CONCLUSIONS AND CLINICAL RELEVANCE: Atopic dermatitis, but not RSV LRTI, is associated with distinct pre-symptomatic differences in the innate immune system. We hypothesize that decreased neonatal IL-10-mediated immune regulation during early life might play a causal role in the initiation of AD.
Assuntos
Dermatite Atópica/imunologia , Dermatite Atópica/fisiopatologia , Regulação para Baixo , Interleucina-10/metabolismo , Receptor 4 Toll-Like/imunologia , Bronquiolite Viral/imunologia , Bronquiolite Viral/fisiopatologia , Bronquiolite Viral/virologia , Citocinas/biossíntese , Feminino , Humanos , Imunidade Inata , Lactente , Masculino , Infecções por Vírus Respiratório Sincicial/imunologia , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/imunologia , Células Th1/imunologia , Receptor 4 Toll-Like/metabolismoRESUMO
BACKGROUND: Neonatal Toll-like receptor (TLR) responses are biased toward Th2-polarizing responses at birth and rapidly mature toward more balanced responses during the first month of life. Postnatal TLR maturation may be guided by environmental exposure. AIMS: To determine the environmental determinants of neonatal TLR function. MATERIALS AND METHODS: A prospective birth cohort study was performed in 291 healthy term neonates. Mode of delivery, breastfeeding, birth month, siblings, pets and parental smoking were analyzed in relation to neonatal innate immune parameters at the age of 1 month. Whole blood concentrations of innate immune cells were measured by flow cytometry. In vitro TLR-mediated cytokine production was determined by ELISA. RESULTS: Breastfeeding was the major determinant of neonatal innate immunity, associated with 5 (31%) of neonatal innate immune parameters, of which the association with TLR7-mediated IL-10 production was most significant (76 pg/ml in breastfed neonates vs. 293 pg/ml in formula-fed neonates, p = 0.001). Of innate immune variables, TLR3-mediated IL-12p70 production was highly associated with environmental exposures (pets, breastfeeding and mode of delivery), whereas TLR9-mediated cytokine responses were not associated with any environmental factor. CONCLUSION: Neonatal innate immune responses are differentially modulated by environmental exposure in the first month of life. The protective effect of breastfeeding against subsequent infections and atopy might be explained by its innate immune modulatory effects in the first month of life.
Assuntos
Aleitamento Materno , Citocinas/sangue , Hipersensibilidade/imunologia , Sistema Imunitário/crescimento & desenvolvimento , Imunidade Inata/imunologia , Receptores Toll-Like/imunologia , Poluição do Ar em Ambientes Fechados/efeitos adversos , Alérgenos/efeitos adversos , Estudos de Coortes , Citocinas/imunologia , Feminino , Humanos , Hipótese da Higiene , Hipersensibilidade/epidemiologia , Sistema Imunitário/imunologia , Recém-Nascido , Interleucina-10/sangue , Interleucina-10/imunologia , Interleucina-12/sangue , Interleucina-12/imunologia , Contagem de Leucócitos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Masculino , Estudos Prospectivos , Poluição por Fumaça de Tabaco/efeitos adversos , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologia , Receptor Toll-Like 9/imunologiaRESUMO
This study investigated the relationship between parental lung function and their children's lung function measured early in life. Infants were participants in the Wheezing Illnesses Study Leidsche Rijn (WHISTLER). Lung function was measured before the age of 2 months using the single occlusion technique. Parental data on lung function (spirometry), medical history and environmental factors were obtained from the linked database of the Utrecht Health Project. Parental data on pulmonary function and covariates were available in 546 infants. Univariate linear regression analysis demonstrated a significant positive relationship between the infant's respiratory compliance and parental forced expiratory flow at 25-75% of forced vital capacity (FEF(25-75%))(,) forced expiratory volume in 1 s (FEV(1)) and forced vital capacity. A significant negative relationship was found between the infant's respiratory resistance and parental FEF(25-75%)and FEV(1). No significant relationship was found between the infant's respiratory time constant and parental lung function. Adjusting for body size partially reduced the significance of the observed relationship; adjusting for shared environmental factors did not change the observed results. Parental lung function levels are predictors of the respiratory mechanics of their newborn infants, which can only partially be explained by familial aggregation of body size. This suggests genetic mechanisms in familial aggregation of lung function, which are already detectable early in life.
Assuntos
Pneumopatias/diagnóstico , Pulmão/fisiologia , Adulto , Pré-Escolar , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Humanos , Lactente , Recém-Nascido , Masculino , Pais , Análise de Regressão , Testes de Função Respiratória/métodos , Mecânica Respiratória , Fatores de Risco , Capacidade VitalRESUMO
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48-96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi-quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT-value and disease severity was found in all RSV cases (rho = -0.52, P = 0.003) and in cases with RSV as the primary pathogen (rho = -0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection.
Assuntos
Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Feminino , Humanos , Lactente , Masculino , Nasofaringe/virologia , Reação em Cadeia da Polimerase , Vírus Sinciciais Respiratórios/genética , Índice de Gravidade de Doença , Carga ViralRESUMO
In this study, we present the multiple detection of respiratory viruses in infants during primary respiratory illness, investigate the sensitivity of nasal swabs and nasopharyngeal aspirates, and assess whether patient characteristics and viral load played a role in the sensitivity. Healthy infants were included at signs of first respiratory tract infection. Paired nasopharyngeal aspirates and nasal swabs were collected. Real-time polymerase chain reaction (PCR) was carried out for 11 respiratory pathogens. Paired nasopharyngeal aspirates and nasal swabs were collected in 98 infants. Rhinovirus (n = 67) and respiratory syncytial virus (n = 39) were the most frequently detected. Co-infection occurred in 48% (n = 45) of the infants. The sensitivity of the nasal swab was lower than the nasopharyngeal aspirate, in particular, for respiratory syncytial virus (51% vs. 100%) and rhinovirus (75% vs. 97%). The sensitivity of the nasal swab was strongly determined by the cycle threshold (CT) value (p < 0.001). The sensitivity of the swab for respiratory syncytial virus, but not rhinovirus, was 100% in children with severe symptoms (score >or=11). It is concluded that, for community-based studies and surveillance purposes, the nasal swab can be used, though the sensitivity is lower than the aspirate, in particular, for the detection of mild cases of respiratory syncytial virus (RSV) infection.
Assuntos
Nasofaringe/virologia , Nariz/virologia , Reação em Cadeia da Polimerase/métodos , Infecções Respiratórias/virologia , Viroses/diagnóstico , Vírus/classificação , Vírus/isolamento & purificação , Comorbidade , Feminino , Humanos , Lactente , Masculino , Infecções Respiratórias/epidemiologia , Sensibilidade e Especificidade , Carga Viral , Viroses/epidemiologia , Viroses/virologiaRESUMO
Newborns are highly susceptible to infectious diseases, which may be due to impaired immune responses. This study aims to characterize the ontogeny of neonatal TLR-based innate immunity during the first month of life. Cellularity and Toll-like receptor (TLR) agonist-induced cytokine production were compared between cord blood obtained from healthy neonates born after uncomplicated gestation and delivery (n=18), neonatal venous blood obtained at the age of one month (n=96), and adult venous blood (n=17). Cord blood TLR agonist-induced production of the Th1-polarizing cytokines IL-12p70 and IFN-alpha was generally impaired, but for TLR3, 7 and 9 agonists, rapidly increased to adult levels during the first month of life. In contrast, TLR4 demonstrated a slower maturation, with low LPS-induced IL-12p70 production and high IL-10 production up until the age of one month. Polarization in neonatal cytokine responses to LPS could contribute to neonatal susceptibility to severe bacterial infection.
Assuntos
Sangue/metabolismo , Citocinas/sangue , Sistema Imunitário/crescimento & desenvolvimento , Interleucina-10/sangue , Interleucina-12/sangue , Lipopolissacarídeos/farmacologia , Receptor 4 Toll-Like/agonistas , Adulto , Sangue/efeitos dos fármacos , Sangue/imunologia , Feminino , Sangue Fetal/citologia , Sangue Fetal/efeitos dos fármacos , Sangue Fetal/imunologia , Sangue Fetal/metabolismo , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Sistema Imunitário/imunologia , Imunidade Inata/imunologia , Recém-Nascido , Interferon-alfa/sangue , Interferon gama/farmacologia , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Interleucina-6/genética , Contagem de Leucócitos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Masculino , Plasma/imunologia , Receptores Toll-Like/agonistas , Fator de Necrose Tumoral alfa/genéticaRESUMO
Although a marked increase in the reporting of wheezing symptoms since the mid-1970s has been described, the underlying immunopathology of the different wheezing phenotypes has not been clarified. Since differences in gene expression might be involved, the objective of the present study was to identify gene expression profiles in CD4+ T-cells from two distinct infant wheezing phenotypes. The gene expression profiles of peripheral CD4+ T-cells were compared by means of microarray analysis of six transient wheezers, six persistent wheezers and seven healthy controls. The differentially expressed genes were subsequently validated by RT-PCR. The differential gene expression profiles reflected common immunological pathways involved in apoptosis or proliferation of T-cells. Furthermore, both wheezing phenotypes showed decreased expression of the complement component 5 receptor 1 gene, a gene involved in the regulation of bronchial responsiveness. Moreover, differences in gene expression profiles were found in genes involved in the immune response against respiratory syncytial virus, such as those encoding signal transducer and activator of transcription 1 and an inflammatory mediator showing enhanced production in asthma (prostaglandin E(2) receptor 2). The present findings suggest that clinical symptoms of wheeze are reflected in common immunological pathways, whereas differences between wheezing phenotypes are, in part, reflected in distinct gene expression profiles.
Assuntos
Linfócitos T CD4-Positivos/metabolismo , Perfilação da Expressão Gênica , Sons Respiratórios/genética , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Masculino , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Receptores de Prostaglandina E/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Asthma can have a negative effect on psychological and social well-being in childhood. Sports participation, school attendance, and quality of life are important issues for children with asthma and their parents. However, a structural evaluation of these factors is not always incorporated in the routine medical approach of children with asthma. Moreover, goals in asthma treatment, such as minimal symptoms and normal activity levels, are achieved in a minority of children. This review describes determinants that are important for the well-being of children with asthma and their parents. Besides the control of symptoms, factors such as sports participation, socializing in peer groups, school attendance, and quality of life must be considered. These issues are relevant when evaluating the management of children and adolescents with asthma. A multidisciplinary evaluation by a pediatrician, school nurse, gym teacher, and psychologist might contribute to an important decrease in the impact of asthma on daily life.
Assuntos
Absenteísmo , Asma/psicologia , Relações Interpessoais , Qualidade de Vida , Esportes , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Meio Ambiente , Nível de Saúde , Humanos , AutoeficáciaRESUMO
The contemporary physician is not merely a professional who is trained in the recognition of clinical syndromes and the application of evidence-based medicine. A good understanding of the basic biomedical sciences is necessary to comprehend what is wrong with a patient and what form of treatment is the most appropriate, especially if a disease manifests itself in an unfamiliar way.
Assuntos
Currículo , Educação Médica/normas , Ciência/educação , Medicina Baseada em Evidências , Humanos , Aprendizagem Baseada em ProblemasRESUMO
To determine the contribution of vascular endothelial growth factor (VEGF) to cerebral edema formation in bacterial meningitis, we used a VEGF neutralizing antibody to block VEGF in rabbits, following induction of meningitis by intracisternal inoculation with 10(9) heat-killed pneumococci. At 8 h, cerebrospinal fluid (CSF) VEGF was significantly elevated in infected untreated animals, and correlated with CSF white blood cell (WBC) count (r=0.56, P=0.004), and brain water content (r=0.42, P=0.04). Blocking of VEGF did not attenuate brain edema, blood-brain barrier disruption, or CSF pleocytosis. The functional role of VEGF in the pathophysiology of BM remains elusive.
Assuntos
Anticorpos Bloqueadores/administração & dosagem , Edema Encefálico/imunologia , Edema Encefálico/fisiopatologia , Permeabilidade Capilar/imunologia , Meningite Pneumocócica/imunologia , Meningite Pneumocócica/fisiopatologia , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia , Animais , Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais Humanizados , Bevacizumab , Edema Encefálico/sangue , Edema Encefálico/líquido cefalorraquidiano , Movimento Celular/imunologia , Cisterna Magna , Feminino , Humanos , Injeções Intravenosas , Leucócitos/imunologia , Leucócitos/patologia , Meningite Pneumocócica/sangue , Meningite Pneumocócica/líquido cefalorraquidiano , Camundongos , Coelhos , Fator A de Crescimento do Endotélio Vascular/sangue , Fator A de Crescimento do Endotélio Vascular/líquido cefalorraquidiano , Equilíbrio HidroeletrolíticoRESUMO
BACKGROUND AND OBJECTIVES: Quality of life measurements can help to estimate the well-being of chronically ill patients, and disclose discrepancies in perception between physicians and patients that might otherwise interfere with the effectiveness of treatment. The objective was to investigate the differences in perception of quality of life between parents of chronically ill children and pediatricians. METHODS: A cross-sectional study was conducted in four tertiary pediatric care centers in The Netherlands. The Health Utilities Index mark 3 (HUI3) was used by 37 pediatricians and 279 parents of patients (children aged 1 to 17 years) with cystic fibrosis admitted either in daycare or for a pneumonia, or patients with newly diagnosed acute lymphoblastic leukemia, juvenile idiopathic arthritis, or asthma. RESULTS: Differences in perception of quality of life between parents and pediatricians appeared to be dependent of the disease. In patients with acute lymphoblastic leukemia (OR 7.4; [95% CI 2.88-18.97], juvenile idiopathic arthritis (4.7; [95% CI 2.00-11.22]), and asthma (2.3; [95% CI 1.13-4.69]) a difference in perception was more likely to occur than in patients with cystic fibrosis admitted in daycare. CONCLUSION: At the onset of a chronic disease, the parents of pediatric patients may be misunderstood by health care professionals, especially in subjective attributes. Assessment of quality of life may contribute to better understanding between pediatricians and parents, and thus may even enhance compliance and treatment effects.
Assuntos
Doença Crônica/reabilitação , Pais/psicologia , Pediatria , Qualidade de Vida , Percepção Social , Adolescente , Artrite Juvenil/fisiopatologia , Artrite Juvenil/psicologia , Artrite Juvenil/reabilitação , Asma/fisiopatologia , Asma/psicologia , Asma/reabilitação , Criança , Pré-Escolar , Doença Crônica/psicologia , Cognição , Estudos Transversais , Fibrose Cística/fisiopatologia , Fibrose Cística/psicologia , Fibrose Cística/reabilitação , Emoções , Feminino , Indicadores Básicos de Saúde , Humanos , Lactente , Locomoção/fisiologia , Masculino , Dor/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/fisiopatologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/psicologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/reabilitação , Fala/fisiologiaRESUMO
OBJECTIVE: In addition to traditional clinical markers, quality-of-life assessment can be helpful to estimate the well-being of patients. Discrepancies in perception of well-being between physicians and patients may interfere with the effectiveness of treatment. A systematic review and meta-analysis were performed to explore the (dis-)agreement in quality-of-life assessments between patients and physicians. STUDY DESIGN AND SETTING: Data on the proportion agreement of paired observations were collected from Medline, Embase, Psychlit, and Social Abstracts. RESULTS: Of the 1,316 articles found, six met the selection criteria, four studied the proportion agreement between children and physicians, and all six the proportion agreement between parents and physicians. None examined the magnitude of over- or underestimation by physicians. The agreement was lower in the more subjective domains (0.54-0.77) in comparison to the more objective domains (0.79-0.94). CONCLUSION: Quality-of-life assessment should be integrated in clinical practice. During long-term treatment the perception of the patients' well-being by physicians and patients themselves can easily diverge from each other, resulting in misunderstandings about the treatment and its usefulness in relation to perceived quality of life, and may even become the base for noncompliance.
Assuntos
Atitude do Pessoal de Saúde , Atitude Frente a Saúde , Indicadores Básicos de Saúde , Qualidade de Vida , Humanos , Médicos/psicologia , Reprodutibilidade dos TestesRESUMO
A neonate with respiratory distress due to a right pneumothorax is presented. After drainage of the pneumothorax, atelectasis of the entire right lung developed. Because the atelectasis persisted, bronchoscopy was performed. On bronchoscopy the carina and right main-stem bronchus could not be visualized. Thoracotomy showed that the right main-stem bronchus was obstructed by a space-occupying lesion that was originating from the right upper lobe. Therefore, a sleeve resection of the right upper lobe was performed, and the right main-stem bronchus was reconstructed. Microscopic examination of the resected right upper lobe showed multiple chondromata. The lesions were located both in the lung parenchyma immediately beneath the pleura and in the bronchial wall. Pulmonary chondromata are rarely diagnosed in children. To our knowledge, this is the youngest patient ever presented with pulmonary chondromata.
Assuntos
Condroma/complicações , Neoplasias Pulmonares/complicações , Insuficiência Respiratória/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Neoplasias Pleurais/complicações , Pneumotórax/etiologia , Atelectasia Pulmonar/etiologiaRESUMO
BACKGROUND: Among the lower respiratory tract infections during infancy requiring hospitalization, respiratory syncytial virus (RSV) bronchiolitis is the most frequent disease entity. Nevertheless treatment remains controversial. METHODS: A poll among the European Society for Paediatric Infectious Diseases (ESPID) members was conducted to determine the respective local and national treatment policies of RSV bronchiolitis. RESULTS: The questionnaire was returned by 88 centers represented in ESPID (response rate 64%). Ribavirin was used occasionally for high risk patients in 34 centers although 16 hospitals follow the guidelines of the Red Book Committee of the American Academy of Pediatrics. There were no centers using ribavirin for all patients. Bronchodilator treatment was used universally in various combinations for all patients in 54 centers and for all high risk patients in 15. Corticosteroids were used by > 80% of ESPID colleagues in various combinations of administration routes. CONCLUSION: The lack of effective treatment for RSV bronchiolitis and the controversy in the literature concerning antiviral, bronchodilator and antiinflammatory therapy leads to inconsistent treatment strategies.
Assuntos
Bronquiolite Viral/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Antivirais/uso terapêutico , Broncodilatadores/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico , Humanos , Lactente , Formulação de Políticas , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Ribavirina/uso terapêutico , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To calculate both medical consumption and socioeconomic effects related to hospitalization for respiratory syncytial virus (RSV) infection in the Netherlands. METHODS: During the winter seasons of 1998 to 2000, parents of all patients hospitalized for RSV in three secondary care hospitals were asked to fill out questionnaires focusing on the 2 weeks before hospitalization, the period in hospital and the 2 weeks after discharge. The questions concerned workdays lost, level of education and current profession, extra childcare needed, consultation by the family physician and drugs prescribed and costs of travelling. RESULTS: Seventy-three children were hospitalized. Median age was 79 days (range, 9 to 537 days), and median weight was 5,295 g (range, 3130 to 10,600 g). Three children were born preterm. Parents had 2 (range, 0 to 6) telephone contacts with the family doctor; the child was seen 2 (range, 0 to 4) times before hospitalization. Parents lost 0.5 workday before hospitalization. Duration of hospitalization was 5 days median (range, 1 to 12 days). Parents lost 1.5 (range, 0 to 9) workdays during hospitalization and drove 118 (range, 6 to 550) miles to visit their child. In the period after discharge expenses were negligible. Calculation of all parameters into currency resulted in a total amount of $2,200 per child hospitalized for RSV. Workdays lost, costs for travelling and consultation of family doctors resulted in $295 per child. CONCLUSIONS: RSV infections necessitating hospitalization in a secondary care hospital have remarkable effects on parental expenses, parental absence from work and medical consumption. On top of the hospital-related costs 15% should be added for parental expenses and socioeconomic costs.
Assuntos
Efeitos Psicossociais da Doença , Hospitalização/economia , Cuidado do Lactente/economia , Infecções por Vírus Respiratório Sincicial/economia , Absenteísmo , Feminino , Custos Hospitalares , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Países Baixos/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Estações do Ano , Fatores Socioeconômicos , Inquéritos e Questionários , Trabalho/economiaRESUMO
BACKGROUND: Gram-negative bacteremia in children, a major cause of morbidity and mortality, may in part be induced by intensive treatment procedures and nonspecific use of antibiotics. Our primary objective was to study the causal relationship between the use of vancomycin and Gram-negative bacteremia, for which this antibiotic is not specifically indicated. METHODS: The study was conducted in a 105-bed tertiary care children's hospital in the period of 1994 to 1997. The study pertains to a cohort of children with suspected bacteremia, in whom a blood culture was performed during hospital stay. Using the bacteriologic laboratory registration system, we selected all pediatric cases with bacteriologically proved Gram-negative bacteremia (n = 105) and a random sample of 225 pediatric controls with negative blood cultures. Using logistic regression analysis we examined associations between Gram-negative bacteremia and the following factors: preceding use of antibiotics, antacids, corticosteroids, surgery, mechanical ventilation, parenteral nutrition, and invasive instrumentation; and the intensity of care assessed with the Therapeutic Intensity Scoring System (TISS 28). RESULTS: Gram-negative bacteremia was positively associated with the use of aminoglycosides, cephalosporins, surgical interventions, central venous catheters, parenteral nutrition, antacids and dexamethasone. The strongest association was with the use of vancomycin (odds ratio, 8.1; 95% confidence interval, 3.1 to 20.9). In a multiple logistic regression model containing all above-mentioned variables, the use of vancomycin remained positively and strongly associated with Gram-negative bacteremia (odds ratio, 3.88; 95% confidence interval, 1.34 to 11.21). Further adjustments and restrictions in the analysis did not materially change these findings concerning vancomycin. CONCLUSIONS: Among children suspected of bacteremia there are several drugs and clinical procedures influencing the risk for Gram-negative bacteremia. Empiric use of vancomycin is strongly and independently associated with Gram-negative bacteremia. The safety of using vancomycin solely on the basis of suspicion of bacteremia in children may not be warranted.
Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Vancomicina/uso terapêutico , Corticosteroides/efeitos adversos , Antiácidos/efeitos adversos , Antibacterianos/farmacologia , Bacteriemia/epidemiologia , Estudos de Coortes , Feminino , Cirurgia Geral , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Razão de Chances , Nutrição Parenteral/efeitos adversos , Análise de Regressão , Respiração Artificial , Fatores de Risco , Vancomicina/farmacologia , Resistência a VancomicinaRESUMO
BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.
Assuntos
Sons Respiratórios/etiologia , Infecções por Vírus Respiratório Sincicial/complicações , Infecções Respiratórias/complicações , Auscultação , Feminino , Seguimentos , Humanos , Lactente , Masculino , Morbidade , Recidiva , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório HumanoRESUMO
Although bacterial superinfection in viral respiratory disease is a clinically well documented phenomenon, the pathogenic mechanisms are still poorly understood. Recent studies have revealed some of the mechanisms involved. Physical damage to respiratory cells as a result of viral infection may lead to opportunistic adherence of bacteria. Enhanced bacterial adherence by specific mechanisms has been documented for respiratory cells infected with influenza A virus, respiratory syncytial virus and adenovirus in both in vitro and in vivo models. To date, results of various experimental studies indicate that different mechanisms for increased bacterial adherence induced by viruses are operating for specific viral-bacterial combinations. In the present review, a number of key findings obtained during the past two decades is presented and discussed.
Assuntos
Infecções Bacterianas/etiologia , Infecções Respiratórias/complicações , Viroses/complicações , Animais , Infecções Bacterianas/microbiologia , Causalidade , Humanos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Viroses/virologiaRESUMO
Antibiotics are among the most commonly prescribed drugs in paediatrics. Because of an overall rise in health care costs, lack of uniformity in drug prescribing and the emergence of antibiotic resistance, monitoring and control of antibiotic use is of growing concern and strict antibiotic policies are warranted. Before such policies can be implemented, detailed knowledge of antibiotic prescribing patterns is important. In this combined retrospective and prospective study the utilisation of antibiotics in a paediatric university hospital over three consecutive years has been analysed. Over an 8-week period (1 November-22 December) in 1994, 1995 and 1996 patient charts were reviewed with regard to antibiotic prescription (generic class, dose, duration and indication). A total of 1120 patients were admitted during the study periods. Antibiotics were prescribed at least once for 36% of hospitalised children, although only 12.3% of the patients receiving antibiotics had a proven bacterial infection. During a single hospitalisation 13, 4.7, 2.6, and 2.7% of all children received 2, 3, 4 or more than four antibiotics, respectively. Infants less than 2 years received antibiotics more frequently than older children (25 and 11% respectively, P=0.0256). More children admitted to the intensive care unit received antibiotics compared with patients admitted on medium care units (49.7 and 29.3% respectively, P < 0.0001). They received more often several different antibiotic courses (2.6 courses per patient versus 1.9 courses per patient, P < 0.0001). These children were also given more often intravenous rather than oral antibiotics (P < 0.0001) Significant differences could be found between the generic classes of antibiotics prescribed to children admitted to the intensive care unit and the medium care. However high variability in dose and duration of antibiotic therapy for the same clinical indication was shown. A high percentage of all hospitalised children receive antibiotics. In most cases antibiotics are started on an empirical basis, without proof of a bacterial infection, either before the start of therapy or afterwards. The fact that children admitted to intensive care units and patients of younger age groups are at special risk of receiving multiple courses of antibiotics, together with the knowledge that antibiotic resistance develops in this setting, suggest that strategies to control antibiotic use should focus on these patient populations.
Assuntos
Antibacterianos/administração & dosagem , Adolescente , Criança , Pré-Escolar , Quimioterapia Combinada , Uso de Medicamentos , Medicamentos Genéricos , Feminino , Hospitais Pediátricos , Hospitais Universitários , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Instituições para Cuidados Intermediários , Tempo de Internação , Estudos Longitudinais , Masculino , Estudos Prospectivos , Estudos RetrospectivosRESUMO
Dutch type periodic fever (DPF) is an autosomal recessive hereditary fever syndrome. Cases have been reported worldwide, the majority from France and The Netherlands. From infancy the patients suffer fever attacks that recur every 2-8 weeks, often precipitated by immunizations, infections or emotional stress. Fever lasts 2-7 days and can be accompanied by malaise, headache, diarrhea, abdominal pain, vomiting, skin rashes, arthralgia, arthritis, tender lymphadenopathy, hepatosplenomegaly, and oral and genital ulcers. Laboratory evaluation during fever shows granulocytosis and elevated acute phase reactants. DPF is caused by a deficiency of the enzyme mevalonate kinase (MK). Besides DPF, the spectrum of MK deficiency includes a severe phenotype, mevalonic aciduria (MA). MA patients have less residual MK activity, leading to substantially higher urinary mevalonic acid excretion than in DPF. Mevalonic aciduria is characterized by mental retardation and dysmorphic features in addition to the clinical features of DPF. At the genomic level, several mutations of varying severity have been identified. The DPF phenotype is caused by one particular mild missense mutation. Most patients are compound heterozygotes for this mutation and a more severe mutation. The mechanism by which MK deficiency leads to fever is not understood. The vast majority of DPF patients have persistently elevated serum IgD and can be classified as having hyperimmunoglobulinemia D and periodic fever syndrome (HIDS). Conversely, most HIDS patients have MK deficiency and hence DPF, but the two disorders do not overlap entirely.