The Impact of Atopic Dermatitis and Corticophobia on the Quality of Family Life.

The aim of the study was to investigate the impact of atopic dermatitis (AD) in children and corticophobia on the quality of family life. Children with AD and their parents were included in a cross-sectional study. The severity of AD was self-assessed using the Patient Oriented-Scoring of Atopic Dermatitis (PO-SCORAD) index, and the severity of corticophobia using the Topical Corticosteroid Phobia (TOPICOP) score, and the general impact of AD on family quality of life using the Family Dermatology Life Quality Index (FDLQI). We included 330 parents, mostly mothers (99.4%) and children with a median age of 3 years (interquartile range, IQR 1.5-5.0 years). The median values of the PO SCORAD index and TOPICOP score were: 19.1 (IQR 13.6-24.1) and 58.3 (IQR 41.7-72.2), respectively. The median FDQLI score was 12 (IQR 7-16). The influence of independent variables such as parental age, child's age, child's gender, family history of allergies, place of residence, parental education, associated allergic disease in the child, PO SCORAD, and the TOPICOP score on the FDLQI was analysed. The significant models were the age of the parents (protective factor), the PO SCORAD index, and the TOPICOP score, which together accounted for 26.1% of the variability of FDLQI. Concusion of the study is that AD in children, its severity, and the parent's fear of chronic corticosteroid treatment impair the quality of family life.

Allergic Diseases and Atopy Among Schoolchildren in Eastern Croatia.

A cross-sectional study was carried out in Brod-Posavina County, Croatia, to assess the prevalence of allergic diseases and atopy, as well as to investigate the possible etiologic factors for asthma, allergic rhinitis and eczema in childhood. The study included 1687 schoolchildren aged 10-11 years. Data were collected using standardized International Study of Asthma and Allergies in Childhood (ISAAC) Phase II written questionnaire. Skin prick tests were performed to provide an objective measure of atopy, defined as skin reactivity to one or more allergens. Lifetime prevalence of wheezing was 22.7%, rhinitis symptoms 22.5%, and eczema symptoms 17.9%. Period prevalence in the past 12 months was 7.9% for attacks of wheezing, 9.9% for rhinoconjunctivitis symptoms, and 10.1% for eczema symptoms. Of the children in which skin prick test was performed, 20.2% were positive for at least one of the allergens used, with house dust mite sensitization being the most frequent one. Risk factors for allergic disease include allergic disease in family, atopy, sensitization to indoor and outdoor allergens, and environmental tobacco smoke exposure at home. International comparison with the results of other ISAAC Phase II studies showed the Brod-Posavina County to be an area with moderate prevalence of atopy and current asthma symptoms.

Genetic variants in endotoxin signalling pathway, domestic endotoxin exposure and asthma exacerbations.

BACKGROUND: We investigated the interaction between genetic variants in endotoxin signalling pathway and domestic endotoxin exposure in relation to asthma presence, and amongst children with asthma, we explored the association of these genetic variants and endotoxin exposure with hospital admissions due to asthma exacerbations. METHODS: In a case-control study, we analysed data from 824 children (417 asthmatics, 407 controls; age 5-18 yr). Amongst asthmatics, we extracted data on hospitalization for asthma exacerbation from medical records. Endotoxin exposure was measured in dust samples collected from homes. We included 26 single-nucleotide polymorphisms (SNPs) in the final analysis (5 CD14, 7LY96 and 14 TLR4). RESULTS: Two variants remained significantly associated with hospital admissions with asthma exacerbations after correction for multiple testing: for CD14 SNP rs5744455, carriers of T allele had decreased risk of repeated hospital admissions compared with homozygotes for C allele [OR (95% CI), 0.42 (0.25-0.88), p = 0.01, False Discovery Rate (FDR) p = 0.02]; for LY96 SNP rs17226566, C-allele carriers were at a lower risk of hospital admissions compared with T-allele homozygotes [0.59 (0.38-0.90), p = 0.01, FDR p = 0.04]. We observed two interactions between SNPs in CD14 and LY96 with environmental endotoxin exposure in relation to hospital admissions due to asthma exacerbation which remained significant after correction for multiple testing (CD14 SNPs rs2915863 and LY96 SNP rs17226566). CONCLUSION: Amongst children with asthma, genetic variants in CD14 and LY96 may increase the risk of hospital admissions with acute exacerbations. Polymorphisms in endotoxin pathway interact with domestic endotoxin exposure in further modification of the risk of hospitalization.

17q12-21 and asthma: interactions with early-life environmental exposures.

BACKGROUND: 17q12-21 polymorphisms are associated with asthma presence and severity across different populations. OBJECTIVE: To extensively investigate the genes in this region among Croatian schoolchildren in a case-control study, taking account of early-life environmental exposures. METHODS: We included 423 children with asthma and 414 controls aged 5 to 18 years. Fifty-one haplotype tagging single-nucleotide polymorphisms (SNPs) were genotyped (GSDMA, GSDMB, ORMDL3, IKZF3, ZPBP2, and TOP2). Data on exposure to smoking and furry pet ownership were collected using a validated questionnaire. Information on severe asthma exacerbations with hospital admission were retrieved from hospital notes. All patients underwent spirometry. RESULTS: We found 2 SNPs (1 novel rs9635726 in IKZF3) to be associated with asthma. Among children with asthma, 4 SNPs (in ZPBP2, GSDMB, and GSDMA) were associated with hospital admissions and 8 SNPs with lung function. One SNP (rs9635726) remained significantly associated with a predicted forced expiratory volume in 1 second after false discovery rate correction. Nine markers across 5 genes showed interaction with early-life environmental tobacco smoke (ETS) exposure in relation to asthma and 2 with furry pet ownership. Among children with asthma, we observed significant interactions between early-life ETS exposure and 3 SNPs for lung function and among early-life ETS exposure, 3 SNPs (in ORMDL3 and GSDMA), and hospital admission with asthma exacerbation. Three SNPs (in ORMDL3) interacted with current furry pet ownership in relation to hospital admissions for asthma exacerbation. CONCLUSION: Our results indicate that several genes in the 17q12-21 region may be associated with asthma. This study confirms that environmental exposures may need to be included into the genetic association studies.

Asthma severity, polymorphisms in 20p13 and their interaction with tobacco smoke exposure.

BACKGROUND: We investigated the association between genetic variation in chromosomal region 20p13-p12 (ADAM33 and flanking genes ATRN, GFRA4, SIGLEC1 and HSPA12B) and asthma. Amongst asthmatics, we then investigated the association between genetic variants and asthma severity. We evaluated the effect of environmental tobacco smoke (ETS) exposure in the context of genetic variants. METHODS: In a case-control study, we recruited 423 asthmatic children and 414 non-asthmatic controls (age 5-18 yr). Amongst asthmatics, we measured lung function and extracted data on hospitalisation for asthma exacerbation from medical records. Early-life ETS exposure was assessed by questionnaire. We included 85 single-nucleotide polymorphisms (SNPs) in the analysis. RESULTS: Seventeen SNPs were significantly associated with asthma; one (rs41534847 in ADAM33) remained significant after correction for multiple testing. Thirty-six SNPs were significantly associated with lung function, of which 15 (six ARTN, three ADAM33, five SIGLEC1 and one HSPA12B) remained significant after correction. We observed a significant interaction between 23 SNPs and early-life ETS exposure in relation to lung function measures. For example, for rs512625 in ADAM33, there was significant interaction with ETS exposure in relation to hospitalisations (p(int)  = 0.02) and lung function (p(int)  = 0.03); G-allele homozygotes had a 9.15-fold [95% CI 2.28-36.89] higher risk of being hospitalized and had significantly poorer lung function if exposed to ETS, with no effect of ETS exposure amongst A-allele carriers. CONCLUSION: We demonstrated several novel significant interactions between polymorphisms in 20p13-p12 and early-life ETS exposure with asthma presence and, amongst asthmatics, a significant association with the severity of their disease.

Genetic variation in vascular endothelial growth factor-a and lung function.

RATIONALE: Given the role of vascular endothelial growth factor (VEGF) in lung development, we hypothesized that polymorphisms in VEGF-A may be associated with lung function. OBJECTIVES: The current study was designed to assess the role of genetic variants in VEGF-A as determinants of airway function from infancy through early adulthood. METHODS: Association between five single-nucleotide polymorphisms (SNPs) in VEGF-A and lung function were assessed longitudinally in two unselected birth cohorts and cross-sectionally among infants. Replication with two SNPs was conducted in adults and children with asthma. We investigated the functionality of the SNP most consistently associated with lung function (rs3025028) using Western blotting to measure the ratio of plasma VEGF-A(165b)/panVEGF-A(165) among homozygotes. MEASUREMENTS AND MAIN RESULTS: In two populations in infancy, C-allele homozygotes of rs3025028 had significantly higher VmaxFRC, forced expiratory flow(50), and forced expiratory flow(25-75) compared with other genotype groups. Among preschool children (age 3 yr), C allele of rs3025028 was associated with significantly higher specific airway conductance, with similar findings observed for lung function in school-age children. For FEV(1)/FVC ratio similar findings were observed among adolescents and young adults (birth cohort), and then replicated in adults and schoolchildren with asthma (cross-sectional studies). For rs3025038, plasma VEGF-A(165b)/panVEGF-A(165) was significantly higher among CC versus GG homozygotes (P ≤ 0.02) at birth, in school-age children, and in adults. CONCLUSIONS: We report significant associations between VEGF-A SNP rs3025028 and parameters of airway function measured throughout childhood, with the effect persisting into adulthood. We propose that the mechanism may be mediated through the ratios of active and inhibitory isoforms of VEGF-A(165), which may be determined by alternative splicing.

The comparison of anthropometrical parameters of the four-year-old children in the urban and rural Slavonia, Croatia, 1985 and 2005.

The aim of the study is to identify the secular trends in the anthropometrical parameters of the 4-year-old children in Slavonski Brod, Slavonia, Croatia, and the nearby rural area by comparing data of height, weight, and mid-arm circumferences from 2005 with the historical control data published in 1985. The cross-sectional study of 342 children, aged 4 years, from Slavonski Brod and the nearby villages was taken in 2005. The body height, weight, and mid-arm circumferences were measured and compared with the historical control data from the study performed in 1985 in the same area using the same methods. The data were compared according to sex and the place of residence. Results show that there were no significant differences in the body height, weight, mid-arm circumference and body mass index (BMI) between the urban and rural children in 2005. The Children in 2005 were significantly shorter (103.7 +/- 8.3 cm vs. 108.3 cm in 1985, P < 0.001, one-sample T test) and had lower weight (17.4 +/- 2.7 kg vs. 17.9 kg, P = 0.001, one-sample T test) compared with their counterparts in 1985. In 2005 there was no significant difference in the body mass index (kg/m2) between girls and boys in total (15.9 +/- 2.12, vs. 16.1 +/- 1.8, p = 0.262, Independent samples t-test). Differences between the urban and rural parameters have disappeared over the last 20 years, which could be assigned to life-style changes in the rural areas.