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      Childhood body mass index and subsequent physician-diagnosed asthma: a systematic review and meta-analysis of prospective cohort studies

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          Abstract

          Background

          Childhood asthma and obesity prevalence have increased in recent years suggesting a potential association. However, the direction of any association is poorly understood and the potential causal-relationship is unknown.

          Methods

          We examined the association between overweight/obesity, defined by body mass index (BMI) <18 years of age, and subsequent physician-diagnosed incident asthma at least one year after BMI assessment. We sought to explore potential effect modification by sex. PubMed and Embase were searched using keywords and restricted to subjects aged 0–18 years. There were no date or language restrictions. From each study we extracted: authors, publication date, location, overweight/obesity definitions, asthma definitions, number of participants, recruitment duration, description of cohort, follow-up time, adjusted effect estimates (with 95% CI) and estimates of subgroup analysis.

          Results

          Six prospective cohort studies which focused on children <18 years of age met criteria for inclusion. The combined risk ratio (RR) of overweight was associated with asthma (RR = 1.35; 95% CI = 1.15, 1.58). In boys, the combined RR of overweight on asthma was significant (RR = 1.41; 95% CI = 1.05, 1.88). For girls, when BMI was defined by Z-score, the combined RR of overweight on asthma was also significant (RR = 1.19; 95% CI = 1.06, 1.34). The combined risk ratio (RR) of obesity was associated with asthma in both boys and girls (RR = 1.50; 95% CI = 1.22, 1.83), in boys only (RR = 1.40; 95% CI = 1.01, 1.93) and in girls only (RR = 1.53; 95% CI = 1.09, 2.14).

          Conclusions

          Overweight and, especially, obese children are at increased risk of subsequent physician diagnosed asthma in comparison to normal weight children. Except for sex, no studies reported any other potential effect modifiers. The observed sex effects were inconsistent.

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          Most cited references40

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          Overweight, obesity, and incident asthma: a meta-analysis of prospective epidemiologic studies.

          Although obesity has been implicated as an asthma risk factor, there is heterogeneity in the published literature regarding its role in asthma incidence, particularly in men. To quantify the relationship between categories of body mass index (BMI) and incident asthma in adults and to evaluate the impact of sex on this relationship. Online bibliographic databases were searched for prospective studies evaluating BMI and incident asthma in adults. Independent observers extracted data regarding annualized asthma incidence from studies meeting predetermined criteria, within defined categories of normal weight (BMI or= 30). Data were analyzed by inverse-variance-weighted, random-effects meta-analysis. Stratified analysis between BMI categories and within sex was performed. Seven studies (n=333,102 subjects) met inclusion criteria. Compared with normal weight, overweight and obesity (BMI >or= 25) conferred increased odds of incident asthma, with an odds ratio (OR) of 1.51 (95% confidence interval [CI], 1.27-1.80). A dose-response effect of elevated BMI on asthma incidence was observed; the OR for incident asthma for normal-weight versus overweight subjects was 1.38 (95% CI, 1.17-1.62) and was further elevated for normal weight versus obesity (OR, 1.92; 95% CI, 1.43-2.59; p<0.0001 for the trend). A similar increase in the OR of incident asthma due to overweight and obesity was observed in men (OR, 1.46; 95% CI, 1.05-2.02) and women (OR, 1.68; 95% CI, 1.45-1.94; p=0.232 for the comparison). Overweight and obesity are associated with a dose-dependent increase in the odds of incident asthma in men and women, suggesting asthma incidence could be reduced by interventions targeting overweight and obesity.
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            Leptin regulates proinflammatory immune responses.

            Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyperphagia, decreased energy expenditure, and obesity. It is unclear, however, whether defective leptin-dependent signal transduction directly promotes any of the conditions that frequently complicate obesity. Abnormalities in tumor necrosis factor alpha expression have been noted in each of the above comorbid conditions, so leptin deficiency could promote these complications if leptin had immunoregulatory activity. Studies of rodents with genetic abnormalities in leptin or leptin receptors revealed obesity-related deficits in macrophage phagocytosis and the expression of proinflammatory cytokines both in vivo and in vitro. Exogenous leptin up-regulated both phagocytosis and the production of proinflammatory cytokines. These results identify an important and novel function for leptin: up-regulation of inflammatory immune responses, which may provide a common pathogenetic mechanism that contributes to several of the major complications of obesity.
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              Status of childhood asthma in the United States, 1980-2007.

              Centers for Disease Control and Prevention data were used to describe 1980-2007 trends among children 0 to 17 years of age and recent patterns according to gender, race, and age. Asthma period prevalence increased by 4.6% per year from 1980 to 1996. New measures introduced in 1997 show a plateau at historically high levels; 9.1% of US children (6.7 million) currently had asthma in 2007. Ambulatory care visit rates fluctuated during the 1990 s, whereas emergency department visits and hospitalization rates decreased slightly. Asthma-related death rates increased through the middle 1990 s but decreased after 1999. Recent data showed higher prevalence among older children (11-17 years), but the highest rates of asthma-related health care use were among the youngest children (0-4 years). After controlling for racial differences in prevalence, disparities in adverse outcomes remained; among children with asthma, non-Hispanic black children had greater risks for emergency department visits and death, compared with non-Hispanic white children. For hospitalizations, for which Hispanic ethnicity data were not available, black children had greater risk than white children. However, nonemergency ambulatory care use was lower for non-Hispanic black children. Although the large increases in childhood asthma prevalence have abated, the burden remains large. Potentially avoidable adverse outcomes and racial disparities continue to present challenges. These findings suggest the need for sustained asthma prevention and control efforts for children.
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                Author and article information

                Contributors
                Journal
                BMC Pediatr
                BMC Pediatr
                BMC Pediatrics
                BioMed Central
                1471-2431
                2013
                13 August 2013
                : 13
                : 121
                Affiliations
                [1 ]Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
                [2 ]Center for Perinatal, Pediatric and Environmental Epidemiology, Yale University, 1 Church Street, 6th floor, New Haven, CT, 06510, USA
                [3 ]Yale School of Medicine and Graduate School, New Haven, CT, USA
                Article
                1471-2431-13-121
                10.1186/1471-2431-13-121
                3751452
                23941287
                4e5322eb-deed-467a-ba59-96dc46ccd9f5
                Copyright ©2013 Egan et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 7 December 2012
                : 7 August 2013
                Categories
                Research Article

                Pediatrics
                asthma,overweight,obesity,body mass index,body weight,pediatric
                Pediatrics
                asthma, overweight, obesity, body mass index, body weight, pediatric

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