Obesity and the prevalence of allergic diseases in schoolchildren

Although the association between obesity and bronchial asthma (BA) has been gaining more attention, few studies have been conducted concerning the relationship between obesity and other allergic diseases. The objective of this study was to determine whether and how childhood obesity is associated with allergic diseases other than BA, such as atopic dermatitis (AD), allergic rhinitis (AR), allergic conjunctivitis (AC), and either AR or AC (AR/AC). A questionnaire was administered to the parents of 50,086 Japanese schoolchildren. Associations between childhood obesity and the various allergic diseases were evaluated by univariate and multivariate logistic models. Significant associations were found between higher body mass index (BMI) and AD (p = 0.03), and lower BMI and AC (p < 0.0001), and AR/AC (p < 0.0001). There was a significantly higher prevalence of BA in girls with obesity (p = 0.009) than in those without obesity. Significantly lower prevalence of AC (p = 0.01) and AR/AC (p = 0.002) among children with obesity, and AR (p = 0.04) and AR/AC (p = 0.0004) among boys with obesity were observed than those without obesity. Those who were obese and had AD were significantly more likely to have severe symptoms (p = 0.01). Overall, childhood obesity has positive associations with BA prevalence and AD severity, whereas it has negative associations with AR and AC prevalence, especially among boys. Changes in the immunologic balance accompanied by obesity might have different effects on each type of allergic disease. Exploring the mechanisms by which childhood obesity affects allergic status should lead to new management options for childhood allergy.     

Inconclusive Cystic Fibrosis neonatal screening results: long-term psychosocial effects on parents

Aim:  Cystic Fibrosis (CF) Newborn Screening occasionally identifies neonates where a CF diagnosis can neither be confirmed nor excluded. To assess how parents of these infants cope with this ambiguous situation.
Methods:  Parents of 11 children with Ambiguous Diagnosis (group AD) were compared with parents of 11 children diagnosed with CF through neonatal screening [group Cystic Fibrosis Diagnosis (CFD)] and with parents of 11 Healthy Control children (group HC) matched for gender and age.
Results:  The emotional reaction to the inconclusive result was less pronounced in AD than in CFD (p = 0.003), and AD parents considered their infants as healthy as controls. Parents' anxiety about their child's health is stronger in CFD than in AD (p < 0.05) and HC (p < 0.001). Long-term emotional distress was rated similarly in AD and CFD, and greater than in HC (p = 0.0003). The parent/child relationship was less influenced in AD than in the CF group (p = 0.03). Seven AD and CFD parents changed their family planning projects.
Conclusion:  Inconclusive neonatal screening results appear to be understood and associated with lower anxiety levels than CF diagnosis. Concern about the child's health is similar to healthy controls and lower than in parents of CF children.     

Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth

Bønnelykke K, Pipper CB, Tavendale R, Palmer CNA, Bisgaard H. Filaggrin gene variants and atopic diseases in early childhood assessed longitudinally from birth.
Pediatr Allergy Immunol 2010: 21: 954–961.
© 2010 John Wiley & Sons A/S Copenhagen Prospective Study on Asthma in Childhood (COPSAC) was one of the discovery cohorts of the association between eczema and variants in the filaggrin coding gene (FLG). Here, we study the FLG‐associated risk of asthma symptoms in early life and describe the temporal relationship in the development of the different FLG‐associated atopic outcomes: asthma, sensitization and eczema, assessed longitudinally from birth. A high‐risk cohort of 411 children was assessed in a prospective clinical study from birth to school‐age. Asthma, acute severe asthma exacerbations, sensitization and eczema were diagnosed prospectively by the investigators. FLG variants R501X and Del4 were determined in 382 Caucasians. Filaggrin variants increased risk of developing recurrent wheeze, asthma and asthma exacerbations (hazard ratio 1.82 [1.06–3.12], p = 0.03), which was expressed within the first 1.5 yr of life. Children with filaggrin variants had a marked and persistent increase in acute severe asthma exacerbations from 1 yr of age (incidence ratio 2.40 [1.19–4.81], p = 0.01) and increased risk of asthma by age 5 (odds ratio 2.62 [1.12–6.11], p = 0.03). FLG variants increased the risk of eczema, manifesting fully in the first year of life (point prevalence ratio for age 0–5 was 1.75 [1.29–2.37]; p‐value = 0.0003) contrasting the increased risk of specific sensitization by age 4 (odds ratio 3.52 [1.72–7.25], p = 0.0007) but not age 1.5. This study describes a FLG‐associated pattern of atopic diseases characterized by the early onset of asthma symptoms and eczema and later development of sensitization. The association of filaggrin variants with asthma suggests skin barrier dysfunction as a novel, and potentially modifiable, mechanism driving early childhood asthma.     

Association of early growth response-1 gene polymorphisms with total IgE and atopy in asthmatic children

Early growth response-1 ( Egr-1 ) is expressed in human airways and found to modulate tumor necrosis factor, immunoglobulin E (IgE), airway responsiveness, and interleukin-13-induced inflammation in mice. We investigated the effects of Chinese-tagging single nucleotide polymorphisms (SNPs) of Egr-1 on asthma traits in 298 Chinese asthmatic children and 175 controls, and a replication community cohort of 191 controls. Tag SNP (−4071 A→G) and three additional SNPs (−1427 C→T, −151 C→T and IVS1 −42 C→T) were genotyped by restriction fragment length polymorphism (RFLP). Significant associations were found between plasma total IgE concentration and −4071 A→G (p = 0.008) and IVS1 −42 C→T (p = 0.027) in asthmatic patients. After Bonferroni correction, only −4071 A→G showed significant association. Multivariate regression analysis confirmed this significant association with a standardized coefficient β of 0.156 (95% CI: 0.046–0.317; p = 0.009) in asthmatics among the three SNPs with age and gender-adjusted. In −4071 A→G, IgE_log was significantly higher in patients with the GG genotype than the AA genotype (p = 0.009). In addition, −4071 A→G was significantly associated with atopy (p = 0.016) and high total IgE concentration (p = 0.030) among asthmatics. Patients with the G allele had a 3.5-fold risk of having atopy and a 2.0-fold risk of having high total IgE concentration than those homozygous for the A allele. This is the first report to show significant association of Egr-1 polymorphisms with plasma total IgE and atopy in asthmatics. It may help to explore the pharmacogenetics of Egr-1 inhibitors.     

肾病综合征合并寻常性鱼鳞病临床特征及相关基因突变研究

目的 研究肾病综合征(nephrotic syndrome,NS)合并寻常性鱼鳞病(ichthyosis vulgaris,IV)患儿的临床特征,探讨FLG基因及NPHS2基因与疾病之间的关系.方法 分析我院3例NS合并IV患儿的临床、病理资料,并采用聚合酶链反应-单链构象多态性、DNA测序法,分析患儿NPHS2基因及患儿和3个家系中的部分IV患者的FLG基因.结果 ①3例NS合并IV患儿(1号女性,2号、3号为男性)对激素及多种免疫抑制剂治疗反应均差,随访观察1.5～4年未缓解.②1号患儿的兄长死于"尿毒症",其他2个家系中无肾脏疾病患者.③初次肾活检,2例为轻度系膜增生性肾小球肾炎,1例为微小病变;其中2例患儿在第1次肾活检的1年半后,重复肾活检,进展为中度系膜增生性肾小球肾炎.④3例患儿及3个家系中部分IV患者均具有FLG基因常见的突变类型R501X 和(或)2282del4,没有发现NPHS2基因突变.结论 3例NS合并IV患儿对激素及免疫抑制剂均耐药,肾脏病理损害进展较快,提示患儿对激素及免疫抑制剂耐药可能与FLG基因相关联.     

Increasing the hospitalization of asthma in children not in adults – from a national survey in Taiwan 1996–2002

Prevalence of asthma has risen gradually in past 30 yr in Taiwan, but less is known about the trend of asthma hospitalization and different hospitalization patterns between children and adult groups in the Chinese population. The implementation of National Health Insurance (NHI) in Taiwan was in 1995, and it covered health care for >96% of the population. Using NHI data from 1996 to 2002, we investigated the admission rate, length of stay, cost and the readmission rate of hospitalization with primary diagnosis of asthma in this period. We also compare the difference between the children group (<18 yr old) and adult group (≥18 yr old). The average incidence of hospitalization in the age group below 18 was 105.0 cases per 100,000 children, and was 116.7 per 100,000 population in the adult group during that period. It increased by 6.5% annually in the children group, though it was 0.1% annually in the adult group. The hospitalization days were 3.6 ± 2.4 days in the children group, and were 8.2 ± 8.9 days of those age ≥18 (p < 0.0001). The hospitalization cost was $288.7 ± $292.9 and $717.5 ± $1409.4, respectively (p < 0.0001). Autumn was the most frequent admission season in the children group, but the winter season was the most common in the adult group. The average readmission rate in this period was 20.4%. It was 13.0% in the children group, and was 22.6% in the adult group (p < 0.0001). The general hospitalization rate of asthma in the children group was lower than the adult group. It increased significantly in the children group from 1996 to 2002, but the admission cost rose prominently in the adult group during the same period. The hospitalization days, admission cost, and readmission rate were also significantly lower in the children group.     

The C−159T polymorphism in the CD14 promoter is associated with serum total IgE concentration in atopic Chinese children

Activation of macrophages through CD14 by microbes is crucial in inducing immunity by type 1 T helper cells. A C-to-T polymorphism at position −159 of CD14 was associated with serum total IgE level in Caucasians but not in Japanese subjects. The objective of this study is to determine whether this polymorphic marker is associated with atopy and asthma phenotypes in Chinese children. Restriction fragment length polymorphism was used to characterize CD14/−159 genotypes. Microparticle immunoassay was used to measure serum total IgE level; fluorescent enzyme immunoassay was performed to measure serum concentrations of specific IgE to aeroallergens; and enzyme-linked immunosorbent assay was used to measure serum levels of soluble CD14 (sCD14). Lung function in asthmatics was assessed by spirometry. Two hundred and fifty-eight patients and 92 control children were recruited. Their mean serum total IgE concentrations were 331 and 74 kIU/l, respectively (p < 0.0001). Atopy, defined as the presence of at least one allergen-specific IgE in serum, was found in 220 (85%) patients and in 41 (45%) controls (p < 0.0001). Serum sCD14 levels were significantly associated with CD14/−159 genotypes (p = 0.004). Atopic subjects with CC genotype in CD14/−159 had the highest serum total IgE levels compared with CT and TT genotypes, with the respective mean values being 661, 427 and 380 kIU/l (p = 0.015). Similarly, a higher proportion of subjects with CC genotype had increased serum total IgE concentration (p = 0.039). This polymorphic marker was not associated with asthma or aeroallergen sensitization in our cohort. Our results suggest that the C−159T of CD14 was associated with serum total IgE concentration in atopic Chinese children.     

IL13 variants are associated with total serum IgE and early sensitization to food allergens in children with atopic dermatitis

Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non‐atopics. The aim of this study was to test the IL13 p.R130Q and c.1‐1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12–24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1‐1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen’s egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48–60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen’s egg. These findings suggest that IL13 variants play a major role not only in non‐cognate but also in allergen specific IgE synthesis.     

Association analysis of brain-derived neurotrophic factor gene polymorphisms in asthmatic children

Brain-derived neurotrophic factor (BDNF) has been described to modulate airway hyper-responsiveness and inflammation and was involved in late allergic reaction in asthma and higher levels of circulating BDNF were present in allergic asthmatics. In BDNF gene, Val66Met and C-270T polymorphisms were described. There were, however, very few studies analyzing BDNF gene polymorphisms in asthma. The aim of this study was to analyze the possible relationship between these two polymorphisms in the BDNF gene and asthma. Fifty-six pediatric asthmatic patients were analyzed, aged from 6 to 18. The diagnosis of atopic asthma was based on clinical manifestation, lung function test and increased immunoglobulin E level, and/or positive skin prick tests. The control group consisted of 109 healthy subjects. The polymorphisms were genotyped with the use of polymerase chain reaction–restriction fragment length polymorphism method. We did not observe an association of Val/Met polymorphism and the presence of asthma. However, we observed that Val allele is much more frequent in the male group of asthmatic patients (p = 0.06). For −270C/T polymorphism, we found significant differences between asthmatic patients and the control group (p = 0.041 for genotypes and p = 0.005 for alleles). The results may suggest a relationship between the BDNF gene and asthma and male gender of asthmatic children.     

FcγRIIIa-V/F 158 polymorphism in Turkish children with asthma bronchiale and allergic rhinitis

Fc receptors (FcR) play an important role in immune regulation. This might be linked to the variability in immune response, therefore relating to the pathogenesis of atopic diseases. The aim of the present study was to evaluate the Fc γ RIIIa gene polymorphism in Turkish children with asthma and allergic rhinitis. The study included 364 atopic children (184 bronchial asthma, 180 allergic rhinitis) and 234 healthy subjects as the control group, aged between 5 to 16 years. Patients were recruited from outpatient clinics of allergy and general pediatric care. Plasma IgE concentrations were measured by immunoassays and skin prick test was done in children with atopic diseases. The Fc γ RIIIa gene polymorphism was determined using the polymerase chain reaction method. Distribution of V158V genotype was significantly different among patient groups compared to controls (for asthmatic children OR: 5.33, 95% CI: 2.80–10.23, p < 0.001; for allergic rhinitis OR: 3.25, 95% CI: 1.75–6.07, p = 0.001). Distribution of 158 V allele was significantly different among asthmatic children (OR: 2.20, 95% CI: 1.65–2.92, p < 0.001) and allergic rhinitis patients (OR: 1.77, 95% CI: 1.32–2.35, p < 0.001) compared to healthy controls. Our study shows that the V158V genotype in Fc γ RIIIa gene polymorphism may be a genetic risk factor for the development of atopic diseases.     

Birth order and sibship size as independent risk factors for asthma, allergy, and eczema

This study was carried out to disentangle the independent relations of birth order and sibship size with the presence of asthma, allergy and eczema. In a retrospective study, 700 families in the Netherlands were selected with index children born in 1988–90. Data were extracted from reports of health examinations at the age of 6 years of these children and their siblings. Birth order, and not sibship size, appeared to be a strong risk factor for allergy (excluding eczema). Children with higher birth order had a lower risk of allergy compared with first-borns (adjusted odds ratios: 0.43, 0.26 and 0.05 for second-, third- and fourth- or higher borns, respectively; p < 0.0001). Allergy including eczema also had a significant relation with birth order (p = 0.01). For asthma there appeared no clear relation with birth order. For asthma a non-significant relationship with sibship size (adjusted for birth order) was found (p = 0.06): first-born children in small sibships were more at risk than those in larger sibships. For allergy and eczema no such trend was observed. In conclusion, birth order is inversely related to the risk of allergy, independent of the size of the sibship.     

Soluble E-selectin and soluble ICAM-1 levels as markers of the activity of atopic dermatitis in children

The expression of adhesion molecules is up-regulated in the skin of atopic dermatitis (AD) patients, and the levels of the soluble adhesion molecules sE-selectin and sICAM-1 have been reported to reflect the endothelial activation in the skin of AD patients. The objective of the study was to investigate the relationship between symptom score and levels of sE-selectin, sICAM-1 and sVCAM-1 before and after 2 weeks of treatment. Eighteen children with an exacerbation of AD were admitted and treated with corticosteroid dilutions under occlusive wet dressings (wet-wrap treatment). Symptom score (objective SCORAD) and levels of sE-selectin, sICAM-1, and sVCAM-1 were assessed before and after 2 weeks of treatment. A significant correlation between the objective SCORAD before treatment and the level of sE-selectin (p < 0.05), but not the level of sICAM-1 (p = 0.7) or sVCAM-1 (p = 0.5) was observed. The treatment resulted in a high degree of remission, which was reflected by a significant decrease in the level of sICAM-1 (p < 0.01), whereas there was only a trend in the level of sE-selectin to decrease (p = 0.08). The level of sE-selectin after 2 weeks of treatment still correlated significantly with the objective SCORAD before treatment (p < 0.005). Soluble E-selectin is a relative objective marker for the severity of AD. SCORAD is a treatment-sensitive symptom of AD, whereas E-selectin may be a more stable underlying systemic representation of AD.     

Wheezing requiring hospitalization in early childhood: Predictive factors for asthma in a six-year follow-up

Although asthma is common after wheezing in early childhood, the risk factors for and the prevention of later asthma are poorly understood. During the present follow-up study, a range of possible predictive factors for school-age asthma was evaluated. The study group consisted of 82 children hospitalized for wheezing at age < 2 years in 1992–93. The baseline data were collected on entry to the study. In 1999, the children were re-examined at the median age of 7.2 years. A structured questionnaire was applied to chart the symptoms suggestive of asthma, and the children were examined clinically. An exercise challenge test, as well as skin prick tests (SPT) to common inhalant allergens, was performed. Asthma was present in 33 (40%) children, 30 (91%) having continuous medication for asthma. The significant asthma-predictive factors, present on entry to the study, were blood eosinophilia (p = 0.0008), atopic dermatitis (p = 0.0089), elevated total serum immunoglobulin E (IgE) (p = 0.0452), and a history of earlier episodes of wheezing in infancy (p = 0.0468). SPT positivity in early childhood was also associated with school-age asthma (p = 0.002). In contrast, respiratory syncytial virus (RSV) identification during the index episode of wheezing played a minor role as a predictive factor for asthma. In conclusion, if hospitalization for wheezing occurs in infancy, more than every third child will suffer from asthma at early school age; the risk is significantly increased with recurrent wheezing in infancy and the development of allergic manifestations.     

Association of TNF-α with severe respiratory syncytial virus infection and bronchial asthma

Tumor necrosis factor (TNF-)α is a proinflammatory cytokine that is important in the innate host defence and thus in the defence of infectious agents. However, in excess it provokes the development of chronic inflammatory diseases. The aim of this study was to test association of TNF with severe RSV bronchiolitis as example of an infectious disease and asthma as representative for a chronic inflammatory condition. The following study populations were genotyped for 4 polymorphisms within TNF-β (rs909253) and TNF-α (rs1799964, rs1799724, rs1800629): 322 asthmatic children, 151 children with severe respiratory syncytial virus (RSV) bronchiolitis and 270 controls. Furthermore, serum TNF-α levels were measured by a FlowCytomix Assay. Asthma showed association with two TNF-α polymorphisms as well as with TNF haplotpyes (p = 0.0050). In contrast, RSV bronchiolitis was associated with TNF haplotypes (p < 0.00001) but not with any single polymorphism. In addition, TNF-α serum levels correlated with rs1799724 (p = 0.034). A genetically mediated up-regulation of TNF-α expression might provoke a pronounced inflammation of the airways and thus a more severe course of RSV infection as well as the onset of asthma. It remains to be elucidated whether severe RSV bronchiolitis starts TNF-α upregulation and is one first step in the direction to asthma later in life, or whether both dieases are independent from each other and supported by TNF-α upregulation.     

Correlation of nitrites in breath condensates and lung function in asthmatic children

We aimed to evaluate the value of exhaled breath condensates in monitoring airway inflammation in childhood asthma before and after high altitude climate therapy.
Forty-eight asthmatic children on regular anti-asthma treatment with a normal FEV₁ and positive skin prick test for house dust mites were recruited. All children had been referred to an alpine clinic for high altitude climate therapy, because of persistent asthmatic symptoms despite use of daily anti-inflammatory treatment. Subjects were assessed on their arrival and before departure from the alpine clinic. Spirometry, bronchial provocation tests and measurements of nitrites in breath condensates were performed.
Median levels of nitrites were significantly higher before than after high altitude climate therapy (1.27 vs. 0.93 μ m ; p = 0.008). In addition, MEF₅₀ improved significantly (p < 0.0005). There was a significant correlation between nitrites in breath condensates and MEF₅₀ (r = −0.63, p < 0.0001), symptoms (r = 0.47, p = 0.0007) and airway hyper-reactivity (AHR) (r = −0.41, p = 0.004).
In summary, we found a reduction in nitrites in breath condensates after a high altitude climate therapy. Significant correlations were found between nitrites and MEF₅₀, AHR and symptoms. We conclude that the measurement of nitrites may be feasible to objectively assess airway inflammation in asthmatic children in order to detect ongoing inflammation in children with normal FEV₁ but persistent symptoms.     

Serum concentration of macrophage-derived chemokine may be a useful inflammatory marker for assessing severity of atopic dermatitis in infants and young children

Chemokines are responsible for the trafficking of leukocytes to sites of inflammation. Serum chemokine levels were previously shown to be increased in adult patients with atopic dermatitis (AD). We tested whether serum concentrations of chemokines, including macrophage-derived chemokine (MDC), thymus and activation-regulated chemokine (TARC), eotaxin (EOX), interferon gamma inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1), are useful inflammatory markers for assessing AD severity in infants and young children. To investigate this, we assessed the severity of AD clinically using the SCORing Atopic Dermatitis (SCORAD) index system. Serum chemokine concentrations were determined by sandwich enzyme immunoassay. Twenty AD patients with a median age of 2.1 years [interquartile range (IQR): 0.6–4.2] were recruited. Their SCORAD score was 23.5 (12.5–33.5). Serum concentrations of MDC, TARC, EOX, IP-10 and MCP-1 were 2551 (1978–3935), 1469 (1125–3070), 68 (57–85), 126 (101−226) and 518 (419–614) pg/ml, respectively. Serum MDC levels correlated with SCORAD (r = 0.608, p = 0.004) and its extent (r = 0.629, p = 0.003) and intensity (r = 0.557, p = 0.011) components. Serum TARC concentration showed weaker correlation with extent (r = 0.474, p = 0.035) and intensity (r = 0.465, p = 0.039) of skin involvement but not SCORAD. The median serum levels of MDC (3131 vs. 2394 pg/ml; p = 0.031) and EOX (80 vs. 61 pg/ml; p = 0.046) were also higher in children with moderate as compared with mild AD. The other chemokines did not correlate with AD severity. In conclusion, our results suggest that serum MDC concentration may be a useful inflammatory marker for assessing AD severity in infants and young children.     

Time trends of the prevalence of asthma and allergic disease in Austrian children

After a substantial increase in the prevalence of atopic disease in Europe, recent studies indicate that a plateau has been reached. However, variation across countries and age groups exists. We studied the prevalence and time trends of asthma and allergic disease among schoolchildren in Austria, a country with traditionally low rates of asthma, hay fever, and eczema. As part of the International Study of Asthma and Allergies in Childhood (ISAAC), symptoms and physician diagnoses of asthma and allergic disease of 13,399 Austrian children aged 6–7 yr and 1516 children aged 12–14 yr were surveyed between 1995 and 1997. A similar survey was conducted between 2001 and 2003. Among children aged 6–7 yr, significant increases were seen in the prevalence of physician-diagnosed asthma (+16%; p = 0.013), hay fever (+22%; p < 0.001), and eczema (+37%; p < 0.001) between 1995 and 2003. These changes were paralleled by an increase in the prevalence of symptoms typical for hay fever (itchy eyes and runny nose), but not by an increase in wheeze. Among children aged 12–14 yr, the lifetime prevalence of diagnosed asthma increased by 32%, of hay fever by 19%, and of eczema by 28% (all, p < 0.001). These changes were paralleled by increases in the prevalence of wheezing as documented by both questions before and after a video showing wheezing children but not by symptoms typical for hay fever such as itchy eyes and runny nose. In conclusion, in Austria, contrary to other European countries, the prevalence of asthma and allergic disease increased among schoolchildren. Additional studies are needed to continue monitoring the dynamics of the prevalence of asthma and allergic disease in Austria and to explore trends in their risk factors.     

A new PTGDR promoter polymorphism in a population of children with asthma

Recently, functional genetic variants of the PTGDR gene have been associated with asthma. The objective of this work was to study polymorphisms of the promoter region of PTGDR and their haplotype and diplotype combinations in a Spanish population of children with asthma. In this study, 200 Caucasian individuals were included. Asthma was specialist–physician diagnosed according to the ATS criteria. The polymorphisms were analyzed by direct sequencing. In the study, the new polymorphism (-613C > T) in the promoter region of PTGDR was analyzed. The CT genotype was more common in controls (17%) than in patients with asthma (1%) (p-value = 0.0003; OR, 0.057; 95% CI, 0.007–0.441). The CCCT CCCC diplotype (promoter positions -613, -549, -441, and -197) was more frequent in the group of patients with asthma [Fisher's p-value = 0.012; OR, 10.24; 95% CI (1.25–83.68)]; this diplotype is unambiguous. To our knowledge, this is the first study of -613C > T PTGDR polymorphism in patients. This analysis provides more complete information on influence of diplotype combinations of PTGDR polymorphisms in asthma.     

DNA damage in children with asthma bronchiale and its association with oxidative and antioxidative measurements

Increased production of reactive oxygen species leading to an imbalance between the oxidative forces and the antioxidant defense systems favoring an oxidative injury has been implicated in the pathogenesis of asthma. The aim of the study was to investigate the peripheral DNA damage, and its association with oxidative and antioxidative measurements in children with asthma bronchiale. The study population contained 42 children with asthma bronchiale and 32 healthy controls. DNA damage was assessed by alkaline comet assay in peripheral lymphocytes. Plasma levels of total antioxidant status (TAS), total peroxide concentration (LOOHs), and total oxidant status (TOS) were determined. In asthma bronchiale patients, DNA damage was significantly higher than in controls (17.9 ± 11.8 AU vs. 1.2 ± 2.0 AU, p < 0.001). Plasma TOS and LOOHs were higher in patients than in healthy controls (13.4 ± 7.0 vs. 9.0 ± 3.5, p = 0.002; 9.9 ± 3.4 vs. 4.4 ± 1.5, p < 0.001, respectively). Plasma TAS level in patients was higher than in healthy controls (5.5 ± 2.5 vs. 1.0 ± 0.6, p < 0.001). DNA damage was correlated with TOS ( r  = 0,616, p < 0.001). The findings indicated that lymphocyte DNA damage level increases in children with asthma bronchiale. Elevated DNA damage may be related to increased oxidative stress. However, the mechanism of this association, and whether it is direct or indirect, remains to be explored.     

Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors

The epidemiology of adverse food reactions (AFRs), including the potentially life-threatening food allergy (FA), in Asia is unclear. AFR is believed to be less prevalent than in Caucasians. This study determines the prevalence, clinical features and risk factors for parent-reported AFR in Chinese pre-school children in Hong Kong. Children aged 2–7 yr living in Hong Kong were recruited through local nurseries and kindergartens to ascertain the occurrence and clinical spectrum of AFR and other atopic disorders. Subjects' parents answered a self-administered questionnaire that was modified and validated based on the International Study of Asthma and Allergy in Childhood. A total of 3827 children from 21 nurseries and kindergartens returned the study questionnaires, and information on AFR was analyzable for 3677 (96.1%) children. The prevalence rates of parent-reported AFR and parent-reported, doctor-diagnosed AFR were 8.1% and 4.6%, respectively, whereas 5.0% of pre-schoolers had doctor-diagnosed asthma. The six leading causes of AFR were shellfish (15.8%), egg (9.1%), peanut (8.1%), beef (6.4%), cow's milk (5.7%), and tree nuts (5.0%). When compared with children born and raised in Hong Kong, children born in mainland China (n = 253) had less parent-reported AFR (4.0% vs. 6.7%; p = 0.016). On logistic regression, parent-reported AFR was associated with younger age (p = 0.010), born in mainland China (p = 0.038), and AFR history in father (p = 0.001), mother (p < 0.001), siblings (p = 0.020), and paternal history of rhinitis (p = 0.044). This study shows that AFR is a common atopic disorder in Hong Kong pre-school children, and prevalence rates are comparable to the Caucasians.