Childhood Atopic Asthma Research Articles

Evidence for an association between plasma platelet-activating factor acetylhydrolase deficiency and increased risk of childhood atopic asthma.

Platelet-activating factor (PAF), which has been implicated in the pathophysiology of inflammation in asthma, is degraded and inactivated by PAF acetylhydrolase (PAFAH). Approximately 4% of the Japanese population lacks plasma PAFAH due to a loss-of-function variant (Val279Phe) in the PAFAH gene. Although lack of PAFAH activity is thought to be a risk factor for asthma, there are conflicting findings concerning association between the Val279Phe variant and asthma. In this study, we conducted transmission disequilibrium tests of 118 Japanese parent-child trios identified through mite-sensitive atopic asthmatic children. A case-control study was also carried out. The Phe279/Phe279 genotype was found more frequently in children with atopic asthma (13%) than in their parents (6%) or in controls (4%). Results of the genotypic transmission test were significant, and the Phe279/Phe279 genotype was transmitted preferentially to asthmatic children. Our data support an association between deficiency in PAFAH activity and atopic asthma.

Association of IFN-γ and IFN regulatory factor 1 polymorphisms with childhood atopic asthma

Background: IFN-γ and related molecules play important roles in the differentiation and function of TH2 cells. Objective: We sought to determine whether IFNG and related genes contribute to any susceptibility to atopic asthma, a representative TH2-dominant disorder. Methods: We investigated the association of IFNG (CA repeat polymorphism within the first intron), IRF1 (GT repeat polymorphism within the intron 7), IFNGR1 (Val 14 Met), and IFNGR2 (Gln 64 Arg) gene polymorphisms with atopic asthma in the Japanese child population. Results: A significant association (P = .0018) was observed between IFNG gene polymorphism and atopic asthma. The tendency was more prominent in patients with age of onset of 3 years or younger (P = .0004) or patients with a family history of allergic diseases (P = .0038). Furthermore, there was a significant association between IRF1 gene whole-allele distribution and atopic asthma (P = .044). The tendency was more prominent in patients with onset at 3 years of age or less (P = .0058). On the other hand, IFNGR1 and IFNGR2 gene polymorphisms showed no association with atopic asthma. Conclusion: These results suggested that among IFNG and related genes, IFNG and IRF1 genes confer genetic susceptibility to atopic asthma in Japanese children. (J Allergy Clin Immunol 2001;107:499-504.)

Childhood Atopic Asthma: Positive Association with a Polymorphism of IL-4 Receptor α Gene but Not with That of IL-4 Promoter or Fc ε Receptor I β Gene

We examined the relative contributions of three representative candidate genes for atopy (Fc ε receptor I β, IL-4, and IL-4 receptor α) to the development of atopic asthma. Four polymorphisms of the three candidate genes including Ile50Val and Gln551Arg of IL-4 receptor α, -590C/T of IL-4 promoter and Glu237Gly of Fc ε receptor I β were studied in 100 patients with atopic asthma and 100 nonatopic controls in the northern Kyushu area in Japan. Among the four polymorphisms of the three candidate genes, the Ile50 allele of the IL-4 receptor α chain gene demonstrated an association with atopic asthma subjects (p = 0.044), especially in patients with onset at 2 years of age or earlier (p = 0.034) and in patients with moderate to severe atopic asthma (p = 0.031). Gln551Arg of IL-4 receptor α, -590C/T of IL-4 promoter and Glu237Gly of Fc ε receptor I β showed no association with atopic asthma. A slight linkage disequilibrium between Ile50Val and Gln551Arg polymorphisms of the IL-4 receptor α chain gene was observed in both patients and nonatopic controls. The identification of additional atopy genes in areas with a certain genetic background is essential for genetic diagnosis and to establish new therapeutic modalities for atopic asthma.

Interleukin‐4, interferon‐gamma and interleukin‐5 in peripheral blood of children with moderate atopic asthma

In asthmatic inflammation, TH2 cells play an important role. TH2 cells specifically secrete cytokines like IL-4 and IL-5. IL-4 stimulates IgE production and IL-5 is involved in hemopoiesis, chemotaxis, priming and activation of eosinophils. IFNgamma, produced by TH1 cells, has an inhibitory action on IgE production. To investigate the TH1/TH2-cell pattern in the cytokine production of peripheral blood of asthmatic children. We determined IL-4, IFNgamma and IL-5 in serum and in supernatants of unstimulated and stimulated (24 h with Concanavaline A) cultures of peripheral blood mononuclear cells (PBMCs) in 22 children with moderate asthma (mean age 9.3 years) and in 17 healthy controls (mean age 10.3 years). All children visited the out-patient department (OPD) where history taking, physical examination and blood sampling took place. Children younger than 8 years of age performed symptom and peak flow registration during 1 week after the visit to the OPD. The number of eosinophils were significantly higher in children with asthma, compared with healthy controls. The concentration of IFNgamma in supernatants of cultures of stimulated PBMCs was significantly lower and the ratio of IL-4/IFNgamma was significantly higher in children with asthma compared with healthy controls. The FEV1 was directly and IgE was inversely related to the concentration of IFNgamma in supernatants of cultures of stimulated PBMCs. IFNgamma may play an important role in the pathophysiology of childhood atopic asthma.

Corticosteroids: effect in childhood atopic asthma

Corticosteroids: effect in childhood atopic asthma

Allergic march in children: Atopic dermatitis in Japanese children with bronchial asthma

Atopic diseases in children often develop in series and atopic dermatitis usually occurs first. To clarify the serial development of atopic dermatitis and bronchial asthma in atopic children in Japan, the present and/or past history of atopic dermatitis in patients with bronchial asthma was examined. Patients ( n = 280) with bronchial asthma in five prefectures in Japan were examined at a mean (± SD) age of 8.2 (± 4.5) years and asked about prior and/or concurrent atopic dermatitis. The mean (± SD) age of the patients at the onset of bronchial asthma was 3.0 (± 2.3) years. There was a present or past history of atopic dermatitis in 54% of the patients, and 47 and 72% of those had developed atopic dermatitis within the first 6 and 12 months of life, respectively. In 86% of the patients with both bronchial asthma and atopic dermatitis, atopic dermatitis developed first. The mean (± SD) duration from the onset of atopic dermatitis to the time of examination was 7.3 (± 4.3) years, and atopic dermatitis had been cured in 49% of the patients within this period regardless of the therapy used. Patients with atopic dermatitis had a higher rate of atopic dermatitis in their families (43%) compared with those without atopic dermatitis (23%). These data show that half of the children with bronchial asthma first develop atopic dermatitis in early infancy and that it is relatively easily cured.

Main mechanisms of therapeutic action in atopic asthma in children.

Immunological disorders are clearly demonstrated in children suffering from the atopic form of bronchial asthma, namely increase in the levels of total and specific IgE and a decrease in the number of T cells. Specific hyposensitization produces, in addition to a good clinical effect, an immunomodulating action which is not restricted to the formation of blocking antibodies but is displayed also by T cell stimulation. Our studies revealed a reduction in the level of prostaglandins E and increase in the content of prostaglandins F-2 as well as a decrease in the cAMP levels in blood serum and urine in the period free of attacks; the demonstrated effect of Euphylline, Intal and Zaditen on these values confirms the expediency of introducing these agents into the therapeutic complex.