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Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children
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.
Linköping University, Department of Molecular and Clinical Medicine, Pediatrics. Linköping University, Faculty of Health Sciences.
2002 (English)In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 13, no 5, 361-367 p.Article in journal (Refereed) Published
Abstract [en]

The hypertonic saline challenge test is the recommended method to assess bronchial hyperresponsiveness in the International Study of Asthma and Allergies in Childhood (ISAAC). The sensitivity of this procedure to assess asthma symptoms, however, has been reported to vary among study centers. The purpose of our study was to evaluate the value of this provocation test in an epidemiological survey in children, and to relate the degree of bronchial hyperresponsiveness to the severity of asthma symptoms. All 11–13-year-old children from 16 randomly selected schools in Linköping, Sweden received a questionnaire regarding respiratory symptoms and allergic disease. Skin prick tests with eight inhalant allergens were performed. In addition, all children with wheeze over the past 12 months (current wheeze) and a random sample of children without current wheeze were invited to perform hypertonic saline provocation tests. A complete data set was available for 170 children, including 50 with and 120 without current wheeze. Bronchial hyperresponsiveness (BHR) was defined as at least 15% decline in FEV1. The degree of BHR was represented by the response/dose ratio, i.e. the fall in FEV1 divided by total dose of inhaled saline. The severity of asthma symptoms was classified by the number of wheezing episodes over the past 12 months. ‘Asthma ever’ was defined by a combination of symptoms in the questionnaires. Children with ‘asthma ever’ and current wheeze were considered as having current asthma. Current atopic asthma was defined as current asthma with at least one positive skin prick test. The sensitivity of the procedure to detect ‘asthma ever’, current asthma and current atopic asthma was 62, 61 and 83%, and the specificity 83, 81 and 60%, respectively. The positive challenge rate was 52, 34, 13 and 7% among current wheezers, previous wheezers, non-wheezers with a history of allergy and healthy children. The degree of bronchial hyperresponsiveness increased with the number of wheezing episodes. Thus, the median and range of the response/dose ratio were 4.8%/ml (2.1–14.8), 2.6%/ml (0.7–8.6) and 1.3%/ml (0.8–2.7), respectively, for children with ≥ 4 episodes, 1–3 episodes and no wheezing episodes over the past 12 months (p<0.001). In conclusion, hypertonic saline provocation test is useful as a tool to detect asthma in epidemiological studies in children. The degree of bronchial hyperresponsiveness, as represented by the response/dose ratio, reflects the severity of asthma symptoms.

Place, publisher, year, edition, pages
2002. Vol. 13, no 5, 361-367 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26544DOI: 10.1034/j.1399-3038.2002.01011.xLocal ID: 11106OAI: oai:DiVA.org:liu-26544DiVA: diva2:247093
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically 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, LennartKjellman, MaxBjörkstén, Bengt

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