C.Y. Li

Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children

Human β-defensin (HBD)-1 is constitutively expressed in the airway, and hBD-1 plays crucial roles in innate immunity against respiratory pathogens. Asthma was associated with DEFB1 polymorphisms in Caucasians. This study investigates whether three single nucleotide polymorphisms (SNPs) in 5′-untranslated region of DEFB1 are associated with asthma phenotypes in Chinese children. Subjects aged 5–18 years were recruited from general pediatric clinics. Plasma IgE concentrations were measured by immunoassays. DEFB1 SNPs were characterized by restriction fragment length polymorphism. In all, 305 asthmatics and 156 controls were recruited. For asthma diagnosis, atopy and plasma total IgE, higher percentages of subjects with these outcomes had the minor alleles −20A and −52G (P=0.041–0.0002). For log-transformed total IgE, the covariate was positive and significant for G-20A under recessive model (P=0.001) and for G-52A under both recessive and codominant models (P=0.008 and 0.035). The recessive model covariate was also positive and significant (P=0.020) for C-44G on peripheral blood eosinophil count. The GCA haplotype of DEFB1 was significantly associated with asthma (odds ratio (95% confidence interval): 1.64 (1.05–2.57); P=0.029). These results suggest that DEFB1 is a candidate gene for asthma and atopy in children.

Nitric oxide synthase polymorphisms and asthma phenotypes in Chinese children.

Background Nitric oxide (NO) is a key factor for balancing T‐helper type 1/T‐helper type 2 immunity. Single nucleotide polymorphisms (SNPs) in nitric oxide synthase (NOS) genes have been associated with atopy and exhaled NO concentrations in Caucasians. We investigated the association between asthma traits and genetic polymorphisms in neuronal NO synthase (NOS1) and endothelial NO synthase (NOS3) in Chinese children.

Study of gene-gene interactions for endophenotypic quantitative traits in Chinese asthmatic children.

Background:  Asthma is a complex disease resulting from interactions between multiple genes and environmental factors. Study of gene–gene interactions could provide insight into the pathophysiology of asthma.

Quality-of-life assessment in Chinese families with food-allergic children

Background Caucasian families with food‐allergic children have a compromised quality of life (QoL) for fear of life‐threatening food reactions. Such data are limited in Asian children. Based on our recent questionnaire‐based survey, 8.1% of young children recruited from local nurseries and kindergartens had parent‐reported adverse food reactions (AFRs).

Identifying uncontrolled asthma in young children: clinical scores or objective variables?

Objective. Several international asthma guidelines emphasize the importance of assessing asthma control. However, there is limited data on the usefulness of available assessment tools in indicating disease control in young asthmatics. This study investigated the ability of Chinese version of Childhood Asthma Control Test (C-ACT) and other disease-related factors in identifying uncontrolled asthma (UA) in young children. Methods. During the same clinic visit, asthma patients 4 to 11 years of age completed C-ACT and underwent exhaled nitric oxide and spirometric measurements. Blinded to these results, the same investigator assigned Disease Severity Score (DSS) and rated asthma control according to Global Initiative for Asthma. Results. The mean (SD) age of 113 recruited patients was 9.1 (2.0) years, and 35% of them had UA. C-ACT, DSS and forced expiratory volume in 1 second (FEV1) differed among patients with different control status (p < 0.001 for C-ACT and DSS; p = 0.014 for FEV1). Logistic regression confirmed that UA was associated with DSS (p < 0.001), PEF (p = 0.002), C-ACT (p = 0.011), and FEV1 (p = 0.012). By ROC analysis, C-ACT and DSS were the best predictors for UA (p < 0.001), followed by PEF (p = 0.006) and FEV1 (p = 0.007). When analyzed by the Classification and Regression Tree (CART) approach, the sequential use of DSS and C-ACT had 77% sensitivity and 84% specificity in identifying UA. Conclusions. C-ACT is better than objective parameters in identifying young Chinese children with UA.

Association between candidate genes and lung function growth in Chinese asthmatic children.

Background Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The Childhood Asthma Management Program reported lung function decline in a significant proportion of Caucasian asthmatic children, but such a relation has not been studied in other populations. Our group recently reported that interleukin‐13 (IL13), interleukin‐4 receptor‐α and thymus and the activation‐regulated chemokine interacted to influence asthma and raised plasma total IgE. However, there has not been any study that has addressed the genetic influences for longitudinal lung function growth.

Urinary leukotriene E4 correlates with severity of atopic dermatitis in children.

Leukotriene E4 (LTE4) is elevated in adults with atopic dermatitis (AD). We evaluated whether urinary LTE4 as a noninvasive marker correlates with clinical indices of disease activity in children with AD. AD patients aged 18 years or younger were eligible for inclusion in the study. Disease severity over the preceding 3 days was evaluated by the SCORing Atopic Dermatitis (SCORAD) index. Severity of AD over the past 12 months was evaluated by the Nottingham Eczema Severity Score (NESS) in Chinese. Urinary LTE4 concentration was measured by competitive enzyme immunoassay. One hundred and twenty‐six children with AD (82 boys and 44 girls) and 45 controls were recruited. The mean ± SD urinary log‐transformed LTE4 concentration in AD patients and controls was 2.94 ± 0.32 and 2.62 ± 0.20 pg/mg creatinine, respectively (P < 0.0001). SCORAD significantly correlated with NESS (r = 0.681, P < 0.0001). There were significant correlations between urinary LTE4 concentration and overall SCORAD score (r = 0.270, P = 0.002) and its extent (r = 0.185, P = 0.038) and intensity components (r = 0.247, P = 0.005), but not with NESS. When compared with mild AD, urinary LTE4 concentrations were higher in patients with moderate‐to‐severe disease (P = 0.049). Urinary LTE4 measurement is noninvasive and may be useful in supplementing the SCORAD for following longitudinal changes in AD severity in children. However, the practical value of this assay in a clinical setting remains to be determined.

PHF11 is not a major candidate gene for asthma or eczema in Chinese children

Positional cloning and candidate gene studies in different Caucasian populations identified the gene encoding plant homeodomain zinc finger protein 11 (PHF11) to be associated with asthma and eczema. Microarray analysis also confirmed increased PHF11 expression in type 1 T‐helper lymphocytes. However, such disease associations are unclear in Asian subjects. This case–control genetic association study investigated the relationship between asthma and eczema phenotypes and tagging single‐nucleotide polymorphisms (SNPs) of PHF11 in Hong Kong Chinese children. Three hundred and nineteen asthmatic children and 236 children with eczema were recruited from hospital clinics and 445 children without any history of allergic disease were recruited as controls from local schools and hospitals. Atopy was defined by the presence of allergen‐specific IgE in plasma or positive skin prick tests with wheal ≥3 mm larger than negative control. Lung function of asthmatics was evaluated by pre‐bronchodilator spirometry. Ten PHF11 SNPs were genotyped by multiplex SNaPshot™ assay. Genotyping call rates were 100% for all SNPs, which also followed Hardy–Weinberg equilibrium. These SNPs were tightly linked in one haplotype block (D′ ≥ 0.95 for nearly all SNP pairs). Physician‐diagnosed asthma was weakly associated with PHF11 +20860 and +22818 (P = 0.032 for both). Atopy was also associated with PHF11 +22398 (P = 0.029). However, none of the PHF11 SNPs was associated with eczema diagnosis and plasma total IgE and spirometric parameters in our patients. Our findings do not support PHF11 to be a major candidate gene for asthma, eczema and aeroallergen sensitization in Chinese children. Pediatr. Pulmonol.