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Inflammatory mediators monitored in urine in asthmatic children with hypertonic saline-induced bronchoconstriction and in healthy controls
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, Allergy Centre. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Hypertonic saline provocation tests have been validated to be useful in the International Study of Asthma and Allergies in Childhood, but the inflammatory mechanisms of hypertonic saline-induced bronchial hyperresponsiveness (BHR) have not been well understood in asthmatic children. Of the 127 children who participated in hypertonic saline provocation tests, all asthmatics with (n = 13) and without BHR (n = 7) as well as all healthy controls without BHR (n = 37) were evaluated with urine samples collected before and one hour after the provocation test. Paired samples were analyzed in 11 asthmatics with and 6 asthmatics without BHR and 18 healthy controls. Urinary histamine, 11ß-PGF and LTE4 were analyzed by EIA and urinary EPX by RIA. The levels of LTE4 increased after the challenge tests, both in the asthmatics (median value: 354.2 pg/mg pre-challenge vs. 628.3 pg/mg post-challenge, p = 0.05) and in the healthy controls (median value: 294.4 pg/mg pre-challenge vs. 460.0 pg/mg post-challenge, p = 0.008). The levels of histamine also increased in the latter (median value: 299.3 µmol/rug pro-challenge vs. 568.8 µmol/mg post-challenge, p = 0.03). However, the levels of 11ß-PGF and EPX were similar before and after the challenge tests both in the asthmatics and in the healthy controls. The inhalation of hypertonic saline induced the secretion of LTE4 and histamine even in healthy children, but the bronchoconstriction did not seem to be induced by the analyzed inflammatory mediators, such as LTE4, 11ß-PGF, histamine and EPX.

National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-84614OAI: oai:DiVA.org:liu-84614DiVA: diva2:560713
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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Mai, XiaomeiNilsson, LennartZetterström, Olle

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