Viral infections, cytokine dysregulation and the origins of childhood asthma and allergic diseases.

BACKGROUND: The origins of asthma and allergic disease begin in early life for many individuals. It is vital to understand the factors and/or events leading to their development. METHODS: The Childhood Origins of Asthma project evaluated children at high risk for asthma to study the relationships among viral infections, environmental factors, immune dysregulation, genetic factors, and the development of atopic diseases. Consequently wheezing illnesses, viral respiratory pathogen identification, and in vitro cytokine response profiles were comprehensively evaluated from birth to 3 years of age, and associations of the observed phenotypes with genetic polymorphisms were investigated. RESULTS: For the entire cohort, cytokine responses did not develop according to a strict T helper cell 1 or T helper cell 2 polarization pattern during infancy. Increased cord blood mononuclear cell phytohemagglutin-induced interferon-gamma responses of mononuclear cells were associated with decreased numbers of moderate to severe viral infections during infancy, especially among subjects with the greatest exposure to other children. In support of the hygiene hypothesis, an increased frequency of viral infections in infancy resulted in increased mitogen-induced interferon-gamma responses at 1 year of age. First year wheezing illnesses caused by respiratory viral infection were the strongest predictor of subsequent third year wheezing. Also, genotypic variation interacting with environmental factors, including day care, was associated with clinical and immunologic phenotypes that may precede the development of asthma. CONCLUSIONS: Associations between clinical wheezing, viral identification, specific cytokine responses and genetic variation provide insight into the immunopathogenesis of childhood asthma and allergic diseases.

The role of rhinovirus in asthma exacerbations.

Rhinoviruses are a major cause of asthma exacerbations in children and adults. With the use of sensitive RT-PCR methods, respiratory viruses are found in approximately 80% of wheezing episodes in children and in approximately one half of such episodes in adults. Rhinovirus is a member of the family Picornaviridae, and acute rhinovirus infections occur predominantly in the upper airway. This virus has also been identified in the lower airway, and it might cause acute wheezing through the production of proinflammatory mediators with a resulting neutrophilic inflammatory response. Precisely how this process leads to increases in airway hyperresponsiveness and airway obstruction is not fully established. However, risk factors for wheezing with colds include asthma and atopy, extremes in age, and perhaps having a deficient TH1 response to rhinovirus. With the use of in vitro models and experimental inoculation studies, significant advances have led to a better understanding of the mechanisms by which rhinovirus infections cause asthma exacerbations. Advances in our understanding of this interaction might provide knowledge that could ultimately lead to specific treatment modalities to prevent and/or treat this significant burden of asthma exacerbations.

Decreased quality of life associated with obesity in school-aged children.

OBJECTIVES: To examine the association between health-related quality of life and body mass index (BMI) in preadolescent school-aged children and to provide the possible risk factors among participant characteristics, BMI status, and health-related quality of life. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analysis of 371 (50% female; 32% minority) children from a community-based sample of 8- to 11-year-olds participating in an ongoing cohort study, excluding those who had sleep apnea or who were born prematurely. Using BMI percentiles for age and sex, 17.5% of the children were considered overweight (BMI > or =95th percentile), 12.4% were at risk for overweight (BMI 85th-94th percentile), 8.1% were relatively underweight (BMI <20th percentile), and the remaining 62.0% were of normal weight (BMI 20th-84th percentile). MAIN OUTCOME MEASURES: Health-related quality-of-life scores as determined by the Child Health Questionnaire-Parent Form 50, dichotomized into the bottom quartile or decile. RESULTS: After adjustment for covariates (host factors and health status measurements), overweight children compared with normal weight children scored lower on the Psychosocial Health Summary (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.6) and on subscales measuring self-esteem (OR, 3.5; 95% CI, 1.9-6.3), physical functioning (OR, 2.8; 95% CI, 1.7-6.8), and effect on the parent's emotional well-being (OR, 2.0; 95% CI, 1.1-3.6). Compared with the normal weight group, children who are at risk for overweight scored significantly lower for physical functioning. CONCLUSION: Overweight children have an increased odds of low scores for several health-related quality-of-life domains, suggesting the importance in considering such dimensions in programs aimed at further understanding obesity in children.