| 1. |
- Böttcher, Malin, 1969-, et al.
(författare)
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Allergen-induced cytokine secretion in atopic and non-atopic asthmatic children
- 2003
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 14:5, s. 345-350
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Tidskriftsartikel (refereegranskat)abstract
- Atopic asthma is characterized by excessive T helper 2 (Th2)-like immunity to allergens in the bronchial mucosa. The Th2-cytokine interleukin (IL)-4 induces IgE production, while the Th2-cytokine IL-5 promotes eosinophilic inflammation in the airways of asthmatics. Most asthmatics are atopic, but a subgroup is non-atopic. We hypothesize that allergen-induced Th2, particularly IL-5, responses can be observed in peripheral blood in both atopic and non-atopic asthmatic children but not in healthy control children. The aim of the present study was to determine IL-4, IL-5, IL-9, IL-10, IL-13 and IFN-γ secretion induced from peripheral blood mononuclear cells (PBMC) by a broad panel of inhalant allergens (timothy, cat, birch, dog and house dust mite) in asthmatic children with and without sensitization. The study included 13 atopic asthmatic, 5 non-atopic asthmatic, and 12 non-atopic non-asthmatic children. PBMC were stimulated with allergens and cytokine production was measured with enzyme-linked immunosorbent assay (ELISA). Higher levels of cat and dog antigen-induced IL-5 release were more commonly observed in both atopic and non-atopic asthmatics than in controls. Children with atopic, but not non-atopic, asthma produced higher levels of allergen-induced IL-4 and IL-9 than controls. Non-atopic asthmatics produced more IL-10 than atopic asthmatics after cat stimulation. High levels of eosinophilia-associated IL-5 responses are induced by cat and dog allergen in both atopic and non-atopic asthmatic children. The Th2 cytokines IL-4 and IL-9 were associated only with atopic asthma, probably due to their IgE-inducing properties.
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| 2. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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Leptin and asthma in overweight children at 12 years of age
- 2004
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 15:6, s. 523-530
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is suggested as a risk factor for asthma, but the mechanisms are unclear. The relationship between obesity and asthma has not been considered in children born with very low-birth weight (VLBW). We hypothesized that overweight was a contributing factor for asthma in VLBW children, and that leptin and leptin-associated cytokines might play roles in overweight-related asthma. Seventy-four VLBW and 64 normal birth weight (NBW) children participated in a 12-yr follow up study assessing asthma and allergy. Twenty-seven (12 VLBW) of the 138 children were overweight according to the proposed international definition. The diagnosis of current asthma was made by a pediatrician. Serum levels of leptin and interferon (IFN)-γ were analyzed by enzyme-linked immunosorbent assay (ELISA). Leptin levels were considerably higher in the overweight than in the non-overweight children (median value: 18.1 vs. 2.8 ng/ml, p < 0.001). In the overweight children, current asthmatics had twice as high levels of leptin as children without current asthma (median value: 30.8 vs. 14.3 ng/ml, p = 0.14), but this was not the case in the non-overweight children. IFN-γ was more often detected in the overweight than in the non-overweight children (61% vs. 12%, p < 0.001), and there was a positive correlation between the levels of leptin and the levels of IFN-γ (Rho = 0.40, p < 0.001). In the VLBW group, the overweight children had a significantly increased risk for current asthma compared with the non-overweight children after adjustment for the neonatal risk factors [adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 1.2-27]. Thus, overweight was associated with asthma in the VLBW children. Our hypothesis remained that leptin might be involved in the pathogenesis of asthma in the overweight children, and IFN-γ might be a pathway in the process of leptin-induced inflammation.
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| 3. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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Urinary inflammatory mediators and inhalation of hypertonic saline in children
- 2005
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 60:1, s. 60-64
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Tidskriftsartikel (refereegranskat)abstract
- Background: The inflammatory mechanisms of hypertonic saline-induced bronchoconstriction are not well understood. Methods: Seventeen asthmatics with (n = 11) and without bronchial hyperresponsiveness (BHR) (n = 6) and 18 randomly selected nonatopic nonasthmatic controls without BHR were evaluated by urine samples collected before and 1 h after hypertonic saline provocation test. Histamine, 11β-PGF2α, and LTE4 were analysed by enzyme immunoassay (EIA) and eosinophil protein X (EPX) by radioimmunoassay (RIA). Results: The levels of leukotriene E4 (LTE4) increased significantly after the challenge tests, both in the asthmatics (median: 354 pg/mg pre-challenge vs. 628 pg/mg post-challenge, P = 0.05) and in the controls (median: 294 pg/mg pre-challenge vs. 460 pg/mg post-challenge, P < 0.01). The levels of histamine also increased significantly in the latter (median: 299 μmol/mg pre-challenge vs. 569 μmol/mg post-challenge, P = 0.03). However, the levels of 11β-PGF2α and EPX did not change significantly after the challenge tests either in the asthmatics or in the controls. Conclusions: The inhalation of hypertonic saline increased urinary excretion of LTE4 both in the asthmatics and in the controls. The slight increase of leukotrienes was enough to induce airway obstruction in some of the asthmatics, because of the hyperresponsiveness in their airways.
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| 4. |
- Annus, T, et al.
(författare)
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Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 31:12, s. 1846-1853
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.
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| 5. |
- Mai, Xiaomei, 1969-
(författare)
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Asthma, bronchial hyperresponsiveness and body weight in children
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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-PGF2α 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-PGF2α 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.
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| 6. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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Asthma, lung function and allergy in 12-year-old children with very low birth weight : a prospective study
- 2003
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 14:3, s. 184-192
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Tidskriftsartikel (refereegranskat)abstract
- We assessed the relationship between very low birth weight (VLBW) (≤1500 g) and the development of asthma, lung function and atopy. The study groups comprised 74 of all 86 (86%) VLBW and 64 of all 86 (74%) matched term children who were prospectively followed for 12 years. A questionnaire on asthmatic and allergic symptoms was completed and skin prick tests, spirometry and hypertonic saline provocation tests were performed at 12 years of age. Cytokine secretion was analysed in stimulated blood leukocyte cultures in 28 VLBW and 23 term children. A history of asthma was more frequent among the VLBW children, as compared with the term children at age 12 (22% vs. 9%, p = 0.046). Among the VLBW children, very preterm birth (gestational age: week 25 to 29) (RR 2.5, 95%CI 1.1–5.8), neonatal mechanical ventilation (RR 2.8, 95%CI 1.2–6.4) and neonatal oxygen supplementation (RR 4.3, 95%CI 1.3–14.0) were significantly associated with a history of asthma by the age of 12 years in univariate analyses. In multivariate logistic regression, neonatal oxygen supplementation ≥ 9 days was the only remaining significant risk factor for a history of asthma (adjusted OR 6.7, 95%CI 1.0–44). The VLBW children who required mechanical ventilation during the neonatal period were more likely to have bronchial hyperresponsiveness than those not requiring mechanical ventilation (60% vs. 28%, p = 0.050). The spirometric values were similar among the VLBW and the term children at 12 years. Very low birth weight was not significantly related to allergic rhinoconjunctivitis, eczema or positive skin prick tests. Furthermore, the levels of IL-4, IL-5 and IFN-γ in stimulated cell cultures were similar in the VLBW and the term children. A history of asthma by 12 years of age was twice as common among the VLBW as the term children, and neonatal oxygen supplementation seemed to be associated with the increased risk. Furthermore, mechanical ventilation during the neonatal period was associated with bronchial hyperresponsiveness at age 12. Very low birth weight per se was not, however, related to atopy.
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| 7. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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Early rapid weight gain and current overweight in relation to asthma in adolescents born with very low birth weight
- 2005
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 16:5, s. 380-385
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Tidskriftsartikel (refereegranskat)abstract
- Early catch-up growth and subsequent overweight are suggested to be associated with later cardiovascular diseases and later type II diabetes. However, the impact of early catch-up growth and childhood overweight on the development of asthma has been less studied, particularly in children born with very low birth weight (VLBW). A birth cohort of 74 VLBW children (birth weight ≤ 1500 g) was followed from birth and investigated on asthma at 12 yr of age. Early rapid weight gain was in one way defined as an increase of weight ≥1 standard deviation score (SDS) at 6 months of corrected postnatal age. Current overweight was defined by body mass index (BMI) exceeding 21.2 and 21.7 kg/m2, respectively, for boys and girls at 12 yr of age. Current asthma was diagnosed by a pediatrician, according to asthma ever in combination with a positive response to hypertonic saline bronchial provocation test and/or wheeze at physical examination at 12 yr old. Being overweight at 12 yr of age was associated with an increased risk for current asthma in the VLBW children [crude odds ratio (OR): 5.5, 95% confidence interval (CI): 1.3-22.2]. After adjustment for early weight gain and neonatal risk, the OR of overweight increased nearly three times (adjusted OR: 15.3, 95% CI: 2.5-90.6). Early rapid weight gain seemed to be inversely associated with current asthma (adjusted OR: 0.49 for an increase of weight equal to 1 SDS, 95% CI: 0.23-1.02, p = 0.06). In addition, early rapid weight gain was inversely associated with the magnitude of bronchial responsiveness at 12 yr (coefficient -1.15, p < 0.01). There was a strong and positive association between overweight and asthma at 12 yr of age in the VLBW children. This strong association had been reduced by early rapid weight gain, possibly via the reduction of bronchial responsiveness. © 2005 Blackwell Munksgaard.
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| 8. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood : phase II
- 2003
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Ingår i: Acta Paediatrica. - 0803-5253 .- 1651-2227. ; 92:10, s. 1144-1148
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children.Methods: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n= 161) and without (n= 296) current wheeze. High BMI was defined as ±75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as ±95th percentile. Children with a BMI >75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests.Results: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0–2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0–3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0–4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0–4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness.Conclusion: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.
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| 9. |
- Mai, Xiaomei, 1969-, et al.
(författare)
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Hypertonic saline challenge tests in the diagnosis of bronchial hyperresponsiveness and asthma in children
- 2002
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 13:5, s. 361-367
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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