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Overweight as a contribution factor for asthma in adolescents born with very low birth weight, and the increased level of leptin in overweight-related asthma
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Obesity is a risk factor for asthma, but the mechanisms are unclear. Childhood-obesity is suggested to be the link between very low birth weight (VLBW) and chronic diseases in adults. Thus, we hypothesized that overweight was a contributing factor for asthma in adolescents born with VLBW, and that leptin and leptinassociated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-year follow-up study assessing asthma and allergy. Twelve of the 74 VLBW and 15 of the 64 NBW children were overweight. The diagnosis of current asthma was made by pediatricians, and serum levels of leptin, IFN-γ, IL-4, IL-6 and TNF-α were analyzcd by ELISA. Overweight was an independent contributing factor for current asthma in children born with VLBW (OR 5.8, 95% CI 1.2-27). Leptin levels were higher in children with than without overweight (18.1 vs. 2.8 ng/mL, p < 0.001). In children with overweight, current asthmatics had somewhat higher levels of leptin than children without current asthma (30.8 vs. 14.3 ng/mL, p = 0.14), but this was not the case in children without overweight. lnterferon-y was more often detectable in children with than without overweight (60.9% vs. 12.4%, p < 0.001). There was a weak correlation between leptin and IFN-γ. However, the levels of IFN-γ, IL-4, IL-6 and TNF-a were similar in children with and without current asthma irrespective of overweight. Thus, overweight was a contributing factor for asthma in the VLBW children. Leptin and IFN-γ might be involved in asthma in the overweight children.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84613OAI: oai:DiVA.org:liu-84613DiVA: diva2:560699
Available from: 2012-10-15 Created: 2012-10-15 Last updated: 2012-10-15Bibliographically approved
In thesis
1. Asthma, bronchial hyperresponsiveness and body weight in children
Open this publication in new window or tab >>Asthma, bronchial hyperresponsiveness and body weight in children
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: In the past few years, the relationship between overweight and asthma has been shown in countries with a Western life-style, but the mechanisms of this relation are only partially understood. Also, very low birth weight (VLBW) babies have immature lung and immune systems, which can conceivably affect the development of asthma and allergy later in life. Bronchial hyperresponsiveness (BHR) is a cardinal feature of asthma. A good and validated method is therefore needed to assess BHR in epidemiological studies in children.

Aims: To assess the sensitivity and specificity of hypertonic saline bronchial provocation test as a tool to identify asthma in epidemiological studies and to elucidate the inflammatory mechanisms. To assess whether overweight and VLBW increase the risk for asthma, BHR and atopy. To assess the role of the adipose-derived hormone leptin and leptin-associated pro-inflammatory cytokines in asthma in overweight children.

Material and Methods: Three groups of children were included. Allergic diseases were defined according to standardized and validated questionnaires. The hypertonic saline provocation test with a standardized methodology was applied to assess BHR. Cytokines were analyzed by ELISA in stimulated cells and in serum. The serum levels of leptin were also analyzed by ELISA. Urinary LTE4, 11ß-PGF and histamine were determined by EIA, and EPX by RIA.

Results: The sensitivity of the hypertonic saline provocation test for identifying asthma was over 60% and the specificity was over 80%. Recurrent wheeze was associated with a high magnitude of BHR. The levels of urinary LTE4 increased after the challenge tests, both in the asthmatics (p = 0.05) and in the healthy controls (p < 0.01). The levels of histamine also increased in the latter (p = 0.03). However, the levels of 11ß-PGF and EPX were similar in the asthmatics and in the healthy controls. Current wheeze was independently associated with high body mass index (BMI) (≥ 75th percentile of sex-specific reference values for Swedish children at 12-year-old). Overweight (≥ 90th percentile) had an even more pronounced effect (adjusted OR 1.9, 95 % CI 1.0-3.6). Leptin levels were considerably higher in children with than without overweight (p < 0.001). Among the overweight children, children with current asthma had higher levels of leptin than children without current asthma (30.8 vs. 14.3 ng/ml), although not significant. Interferon-y was more often detected in children with than without overweight (61% vs. 12%, p < 0.001), and there was a weak positive correlation between leptin and IFN-γ. A history of asthma up to 12 years of age was more frequent in the VLBW than in the term children (p < 0.05). In the VLBW children, neonatal oxygen supplementation seemed to be the only independent risk factor for a history of asthma (adjusted OR 4.2). The VLBW children who required neonatal mechanical ventilation were more likely to have BHR at age 12 than those who did not (60% vs. 28%, p = 0.05). However, very low birth weight was not associated with allergic rhinoconjunctivitis, eczema or positive skin prick tests, and the levels of IL-4, IL-5 and IFN-γ in stimulated cell cultures were similar in the VLBW and the term children.

Conclusions: Hypertonic saline provocation tests are useful for identifying asthma in population-based studies in children. Inhalation of hypertonic saline induces the secretion of leukotrienes and histamine even in healthy individuals with no clinical consequences, but the bronchoconstriction does not seem to be induced by the analyzed inflammatory mediators. High BMI and overweight are associated with asthma symptoms. Leptin and leptin-associated pro-inflammatory cytokines, such as IFN-γ, may be involved in overweight-related asthma. Very low birth weight is associated with asthma in adolescence, and neonatal oxygen supplementation seems to be the risk factor. Neonatal mechanical ventilation is related to BHR. However, very low birth weight is not associated with atopy. Thus, very low birth weight may lead to non-atopic, rather than atopic asthma.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 72 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 806
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26663 (URN)11229 (Local ID)91-7373-498-5 (ISBN)11229 (Archive number)11229 (OAI)
Public defence
2003-10-03, Elsa Brändströmssalen, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-15Bibliographically approved

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