Maternal psychologic problems increased the risk of childhood atopic dermatitis.

BACKGROUND: Little is known about the effect of postnatal maternal psychologic problems on the development of childhood atopic disorders. OBJECTIVES: To assess the association between early life maternal psychologic problems and atopic dermatitis (AD) in children in a national birth cohort. METHODS: We used multistage, stratified systematic sampling to recruit 24,200 mother-newborn pairs from the Taiwan national birth registration. Maternal psychologic problems and potential confounders were gathered by the standard questionnaire at 6 months old. At 3 years of age, information about the development of AD was assessed by International Study of Asthma and Allergies in Childhood via home interviews. Multiple logistic regression analysis was performed to estimate the association of postnatal maternal psychologic problems (postpartum depression (PPD) and maternal mental health index) and AD. RESULTS: The prevalence of physician-diagnosed AD was 10.5%. PPD increased the risk of subsequent physician-diagnosed AD in children after adjusting for potential confounders and other maternal mental health index (aOR = 1.42, 95% CI = 1.21-1.66). We observed that the risk of AD associated with PPD was not confounded by other social demographic factors such as maternal AD, maternal education, family income, breastfeeding, day care, and number of siblings. CONCLUSIONS: Postpartum depression increased the risk of childhood AD even when other maternal mental health index and social demographic factors are considered. Early intervention of PPD might be helpful for AD prevention.

Children with atopic dermatitis show clinical improvement after Lactobacillus exposure.

BACKGROUND: The role of probiotics in the treatment of atopic dermatitis (AD) is not clearly established. Further clinical trials with new probiotic formulations are warranted. OBJECTIVES: To assess the effects of Lactobacillus paracasei (LP) and Lactobacillus fermentum (LF), and their mixture on the disease severity, quality of life, and immune biomarkers of children with AD. METHOD: A double-blind, prospective, randomized placebo-controlled study was conducted on 220 children aged 1-18 years with moderate-to-severe AD (Trial number: NCT01635738). The children were randomized to receive LP, LF, LP + LF mixture, and placebo for 3 months. Changes in severity scoring of atopic dermatitis (SCORAD), Family Dermatology Life Quality Index (FDLQI), and Children's Dermatology Life Quality Index (CDLQI) scores in the different groups and at different visits were evaluated. Skin prick tests, levels of IgE, IFN-γ, IL-4, TGF-ß, and TNF-α, and urine biomarkers were also evaluated. RESULTS: Children who received LP, LF, and LP + LF mixture showed lower SCORAD scores than the placebo group (P < 0.001), and this difference remained even at 4 months after discontinuing the probiotics. The FDLQI and CDLQI scores were lower in the LP, LF, and LP + LF mixture group than in the placebo group (P = 0.02 and 0.03). IgE, TNF-α, urine eosinophilic protein X, and 8-OHdG levels decreased, whereas IFN-γ and TGF-ß increased in the probiotic groups, but these did not reach statistical significance except for IL-4 (P = 0.04). In subgroup analyses, SCORAD scores significantly decreased after probiotic treatment especially in children younger than age 12, with breastfeeding > 6 months, and with mite sensitization (P < 0.001). CONCLUSION: Supplementation of a probiotic mixture of LP and LF is associated with clinical improvement in children with AD.

Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis.

BACKGROUND: The biological mechanisms of how prenatal smoke exposure leading to atopic disorders remain to be addressed. Whether prenatal smoke exposure affects DNA methylation leading to atopic disorders is not clear. OBJECTIVE: As most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure induces cord blood DNA methylation. METHODS: Methylation differences associated with smoke exposure were screened by Illumina Infinium 27K methylation arrays for 14 children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors was collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen. RESULTS: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p = 0.018). TSLP gene was further investigated in a larger sample of 150 children from the cohort who completed the follow-up study. Methylation status of the TSLP 5'-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR = 3.17, 95% CI = 1.63-6.19) and with AD (OR = 2.32, 95% CI = 1.06-5.11). The degree of TSLP 5'CGI methylation inversely correlated with TSLP protein expression levels (r = -0.45, P = 0.001). CONCLUSIONS & CLINICAL RELEVANCE: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation.

Maternal employment and atopic dermatitis in children: a prospective cohort study.

BACKGROUND: Considering the early onset of atopic dermatitis (AD), which most often arises in the first year of life, risk factors occurring very early in life must be considered. Little is known about the effects of maternal occupational exposure on the development of atopic disorders in children. OBJECTIVES: The aim of this study was to evaluate associations between maternal employment and childhood AD. METHODS: We used multistage stratified systematic sampling to recruit 24,200 mother-newborn pairs from the Taiwan national birth register. Information on maternal occupation categories, work stress, working time, shift work and potential confounders during pregnancy was gathered by questionnaires after birth. At 3 years of age, information on the development of AD was assessed by home interviews. Multiple logistic regression analysis was performed to estimate the association of maternal employment and AD. RESULTS: Overall, 11,962 out of 19,381 mothers (61·7%) worked during pregnancy. The children of mothers who worked during pregnancy had an increased risk of AD compared with those whose mothers did not work [odds ratio (OR) 1·38, 95% confidence interval (CI) 1·25-1·53]. The children of mothers with a professional or technical occupation had a higher risk of AD (OR 1·64, 95% CI 1·44-1·87). The risk of AD was found to increase with maternal work stress during pregnancy in a dose-response manner (P(trend)<0·01). The mothers of children with AD had a longer working time than those without AD (P<0·0001). However, no significant association between AD and maternal shift work was found. CONCLUSIONS: Working in professional or technical occupations increased the risk of childhood AD in addition to work stress during pregnancy.

A hierarchical Bayesian approach for risk assessment of melamine in infant formula based on cases of related nephrolithiasis in children.

Although the 2008 outbreak of nephrolithiasis in children due to melamine-contaminated infant formula has subsided, it remains uncertain whether the present tolerable daily intake (TDI) of melamine provides sufficient protection for young children. To conduct a safety assessment for melamine in infant formula, we established a dose-response relationship based on 13 nephrolithiasis cases selected from 932 children, all of whom were under 5 years of age and had potentially been exposed to contaminated milk in China or Taiwan. According to the children's exposure history, distributions of individual daily melamine intake (mg/kg BW/day) were reconstructed using Monte Carlo simulations to account for uncertainties in exposure duration and melamine concentrations in the contaminated milk. Based on the simulated individual average daily intake (AVDI) of melamine, subjects were further classified into four separate AVDI groups: high, medium, low and a reference group. A statistical logistic model was then fitted for the dose-response relationship between nephrolithiasis incidence and daily melamine intakes using Markov chain Monte Carlo (MCMC) simulations. Based on the background exposure, spontaneous rate, and mode of action (MOA) of nephrolithiasis in children, the simulated lower bounds of the 95% CIs daily melamine intake ranged from 0.008 to 0.03 mg/kg BW/day corresponding to an additional risks of 0.1% is proposed as a plausible TDI, which is approximately an order lower than the current WHO-suggested TDI level of 0.2 mg/kg BW/day. More stringent regulations on melamine levels in infant formula should be considered to protect young children fully.

Filaggrin polymorphism P478S, IgE level, and atopic phenotypes.

BACKGROUND: Whether environmental exposures may modulate the effect of the skin barrier gene on atopic dermatitis (AD) remains to be elucidated. OBJECTIVES: To determine whether filaggrin (FLG) variants can serve as a predictor for atopic disorders in Chinese individuals and if allergen exposures may modify the effect of FLG variants on AD by total IgE levels. METHODS: In total, 116 children aged 2-5years with AD and 212 control subjects were analysed for the FLG variants using DNA sequencing. Multiple logistic regression models were performed to estimate the association among FLG polymorphisms and atopic phenotypes. Serum total IgE level, standing for the degree of allergen exposures, was later stratified to determine the effects of FLG polymorphisms on AD. RESULTS: A significant difference in genotype frequency was found among AD cases and controls in FLG P478S polymorphism. FLG P478S GG genotype significantly increased the risk of AD [odds ratio (OR) 4·60, 95% confidence interval (CI) 1·88-11·24]. In addition, among subjects with AD, GG genotypes also significantly increased the risk of developing asthma (OR 4·68, 95% CI 1·37-16·03). Further, a similar result was obtained for allergic rhinitis (OR 3·23, 95% CI 1·01-10·30). Interestingly, the P478S GG genotype was significantly related to AD (OR 5·67, 95% CI 1·93-16·60) in children with IgE level ≥100 kU L(-1) . However, the association was not evident when IgE level was < 100 kU L(-1) . CONCLUSIONS: Our results suggest that the FLG P478S polymorphism may confer susceptibility to the development of AD among Chinese individuals and may be modified by IgE levels.

Glutathione S-transferase, incense burning and asthma in children.

Incense burning is a popular practice in many family homes and temples. However, little is known about the effects of indoor incense burning and genetic polymorphisms on asthma. This study evaluated the effects of indoor incense burning and glutathione S-transferase (GST) genetic polymorphisms on asthma and wheeze. In 2007, 3,764 seventh-grade schoolchildren (mean±sd age 12.42±0.65 yrs) were evaluated using a standard questionnaire for information about respiratory symptoms and environmental exposures. Multiple logistic regressions were performed to assess the association between GST polymorphisms and incense burning frequency on asthma and wheeze, after adjusting for potential confounders. The frequency of incense burning at home was associated with increased risk of current asthma (p=0.05), medication use (p=0.03) and exercise wheeze (p=0.001). GST1 (GSTT1) null genotypes were associated with current asthma (OR 1.43, 95% CI 1.00-2.04) and medication use (OR 1.46, 95% CI 1.01-2.22). GSTT1 showed a significant interactive effect with incense burning on current asthma, current wheeze and nocturnal wheeze. The frequency of incense burning was associated with increased risk of current asthma, medication use, lifetime wheeze, nocturnal wheeze and exercise wheeze in an exposure-response manner among children with GSTT1 null genotype (p<0.05). Incense burning is a risk factor for asthma and wheezing, especially in GSTT1 genetically susceptible children.

The association of clinical findings and exposure profiles with melamine associated nephrolithiasis.

BACKGROUND: Little is known about the exposure profiles of melamine in children. We evaluated the association of clinical findings, exposure patterns and biomarkers with nephrolithiasis in children with potential exposure to melamine. METHODS: A case-control study was conducted in children aged 0-16 years with potential exposure to contaminated dairy products. Cases were defined as nephrolithiasis detected by renal ultrasonography. On the basis of different brands of contaminated dairy products consumed, subjects were classified into high exposure, low exposure and control groups with estimated melamine exposure levels of higher than 2.5 ppm, 0.05-2.5 ppm and lower than detection limits <0.05 ppm. We measured urine melamine for those with nephrolithiasis and age-matched and gender-matched controls within the subset of the study population. RESULTS: The duration of consumption of contaminated products was longer in children with nephrolithiasis in the high exposure group than in controls (median (IQR) 12.0 (3.3-24.0) vs 6.0 (4.0-7.0) months; p = 0.048). High melamine exposure levels were significantly associated with nephrolithiasis (OR 61.04 (95% CI 12.73 to 292.84)). The risk was found to increase with estimate melamine exposure levels (p for trend <0.001). Two among 10 affected subjects with nephrolithiasis showed elevated urine melamine levels. In comparison, levels of all 20 controls were lower than the detection limit. CONCLUSIONS: The risk of melamine-associated nephrolithiasis was related to duration of consumption of contaminated products and estimated melamine exposure levels. Though urine melamine was not a sensitive test, it might serve as an exposure biomarker in melamine-associated nephrolithiasis.

Neuro-mediators as predictors of paediatric atopic dermatitis.

BACKGROUND: Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro-mediators remains to be elucidated. OBJECTIVE: To evaluate nerve growth factor (NGF) and vaso-active intestinal peptide (VIP) in predicting paediatric AD and assess their correlation with intrinsic and extrinsic types of AD. METHODS: We performed a nested case-control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow-up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentrations of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by ELISA. Receiver-operating characteristic (ROC) curves were generated to see how well each biomarker could predict AD. RESULTS: The NGF levels were significantly higher in AD patients than controls (mean+/-SD: 65.47+/-44.45 vs. 49.21+/-12.18 pg/mL for cord plasma and 89.68+/-41.04 vs. 66.96+/-23.05 pg/mL for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting paediatric AD (area under the ROC curve=0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18+/-48.15 pg/mL) and extrinsic (86.18+/-37.23 pg/mL) types of AD compared with controls (66.96+/-23.05 pg/mL) (P<0.05). We assessed a significant correlation between self-reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02). CONCLUSION: Our results suggest that NGF is a good alternative biomarker in predicting children with a risk of AD.

Trends in blind and low vision registrations in Taipei City.

PURPOSE: To determine the overall reported incidence and causes of registrable blindness and low vision in Taipei, Taiwan, that have occurred in the previous 10 years. METHODS: Study data were obtained from disability identification registration forms completed between January 1995 and December 2004. Definitions of low vision and blindness were defined by WHO criteria: low vision included visual acuity worse than 6/18 (20/60) to a lower limit of 3/60 (20/400). Blindness was defined as visual acuity worse than 3/60 (20/400) in the better eye with best possible correction. RESULTS: There were 3151 registrations for visual impairment during the study period. A total of 239 registrations were excluded due to insufficient data. Of the remaining 2912 (1518 males and 1394 females), 640 males and 647 females were legally blind (44.20%). A total of 878 males and 747 females were partially sighted. The six leading causes of low vision and blindness, in decreasing frequency, were glaucoma, optic neuropathy, diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and myopic macular degeneration. CONCLUSIONS: The proportions of new registrations owing to glaucoma, diabetic retinopathy, age-related macular degeneration, and myopic macular degeneration have changed significantly since 2000; the proportion due to diabetic retinopathy has increased.

Seroprevalence and risk factors for human papillomavirus in Taiwan.

The aim of the study was to tailor a future Human papillomavirus (HPV) vaccine campaign and to help perform early primary prevention of HPV infection in Taiwan, where the incidence of cervical cancer is high. A cross-sectional survey was conducted of 826 female students, ages 10, 13, 16 and 19-22 years. A self-administered questionnaire was used to collect information on risk factors for HPV infection. Serum samples were tested for antibodies to HPV 16 capsids using a virus-like particle-based enzyme-linked immunosorbence assay. The age-adjusted odds ratio of HPV seropositivity was calculated for each risk factor by multiple logistic regression analysis. HPV 16 antibodies were detected in 13 (1.6%) of 826 participants. The HPV 16 seroprevalence was 0.35% (1/287), 0.85% (2/235), 3.2% (6/185) and 3.4% (4/119), respectively, for age groups of 10, 13, 16 and 19-22 years. In the multiple regression analysis, the history of having sexual activity was the most significant risk predictor for HPV 16 seropositivity. The seroprevalence of HPV 16 increased dramatically among high school seniors and university students, and was significantly associated with sexual activity. Vaccination against HPV is suggested to be undertaken in early adolescence, before 16 years of age and prior to sexual debut.

Environmental risk factors for early infantile atopic dermatitis.

Previous studies of predictors of atopic dermatitis (AD) in Asia have had limited sample size and small numbers of variables focused primarily on family history or dietary exposures. The purpose of this study was to evaluate the influence of various environmental risk factors for early infantile AD. We used multistage, stratified systematic sampling to recruit 2048 mother-child pairs from the Taiwan national birth registration in 2003. Information on environmental risk factors for infant AD gathered by questionnaire were available from 1760 infants at 6 months of age. Multiple logistic regression was used to estimate adjusted odds ratios (aORs) and their 95% confidence intervals (CIs) for risk factors for AD after adjusting for potential confounders. AD was noted in 118 of 1760 (6.7%) of the infants. After adjusting for maternal age and education, family history of atopy, infant gender, and gestational age, fungi on walls of the house [aOR 2.14 (95% CI 1.41-3.22)] and frequent use of microwave oven at home [aOR 1.71 (95% CI 1.13-2.58)] increased the risk of early infantile AD. This study suggests that environmental factors do play a role in early infantile AD. Fungi, a kind of aeroallergen, are especially important in humid climate as in Taiwan and their impacts might be felt at the early infant stage. The hazards of microwave use should be paid more attention.

A comparison of the effect of carbomer-, cellulose- and mineral oil-based artificial tear formulations.

PURPOSE: To compare the efficacy, safety, and local tolerance between carbomer-based artificial tears, cellulose-, and mineral oil-based artificial tears. METHODS: A randomized, open-label, parallel-group comparative 28-day study was designed for 67 patients who were randomized into three treatment groups. Measurements included the scoring of total subjective symptoms and objective signs, Schirmer-Jones test values, and tear break-up time (BUT) at baseline, and after 2 and 4 weeks of treatment. Safety of study treatment was also assessed. Outcomes measured at baseline and 2 and 4 weeks follow-up included the scoring of total subjective symptoms and objective signs, Schirmer-Jones test values, and tear BUT, subjective assessments, and safety. RESULTS: There were no differences regarding total scores, Schirmer-Jones test, or tear BUT at baseline among these three groups at 2 and 4 weeks. Patients in all three treatment groups experienced a significant improvement from baseline in total scores and Schirmer-Jones test values after treatment. Subjective assessment was better with carbomer-based treatment. CONCLUSIONS: Each artificial tear formulation successfully relieved symptoms and signs of keratoconjunctivitis sicca. The tolerance of carbomer-based artificial tears was comparable to that of cellulose- and mineral oil-based artificial tears.

Immunohistochemical study of subepithelial haze after phototherapeutic keratectomy.

PURPOSE: Subepithelial haze is a frequent complication and is often the cause of regression after photorefractive keratectomy (PRK). The lack of understanding of this undesirable complication following PRK is in part due to the limited availability of suitable tissues for pathological studies. METHODS: We examined the expression of various extracellular components in the cornea of a 46-year-old man who underwent phototherapeutic keratectomy (PTK) to remove a central corneal scar secondary to trauma. The patient subsequently underwent penetrating keratoplasty. A scar-free region containing an area of slight subepithelial haze adjacent to normal cornea was used for immunohistochemical staining with antibodies directed against cytoskeletal proteins, ie, vimentin, desmin and smooth muscle actin, and the extracellular components, laminin, heparan sulfate, keratan sulfate, and collagen types III, IV, V, and VII. RESULTS: Immunohistochemistry revealed that basal epithelial cells expressed components of basement membrane. The stromal fibroblasts within the haze tissue were labeled by anti-smooth muscle actin antibodies, a characteristic of myofibroblasts, which synthesized and secreted extracellular matrix components that contributed to the formation of the disorganized collagenous matrix and may account for subepithelial haze. CONCLUSIONS: The expression patterns for the cytoskeletal proteins and extracellular components indicated that the formation of subepithelial haze is a process of tissue remodeling, involving both corneal basal epithelial cells and keratocytes during wound repair.

Clinical and specular microscopic manifestations of iridocorneal endothelial syndrome.

PURPOSE: To investigate the correlation between the clinical pictures and the specular microscopic findings in patients with iridocorneal endothelial (ICE) syndrome. METHODS: The records of 15 patients with ICE syndrome who presented at the National Taiwan University Hospital between 1993 and 1996 were examined. The medical history, clinical pictures of the cornea, iris and anterior chamber angle, intraocular pressure, specular microscopic findings, and the correlation between clinical and specular microscopic findings were assessed. RESULTS: Endothelial changes in specular micrographs were found in all the patients, even in those patients with minimal angle involvement by peripheral anterior synechiae. Corneal decompensation resulting in corneal edema and bullae formation was the main cause of visual impairment. Neither ICE grading nor endothelial cell density correlated with corneal edema or intraocular pressure, but they correlated with the angle involvement in ICE syndrome. The intraocular pressure was difficult to control in 8 of these patients, even after treatment with anti-glaucoma agents and trabeculectomy, especially in the patients with Cogan-Reese syndrome. CONCLUSION: Although specular microscopy provides an invaluable method for the diagnosis of ICE syndrome, it is not a reliable tool for predicting prognosis. Close follow-up of intraocular pressure and early detection of glaucoma are important steps to preserve visual functions in patients with ICE syndrome.

Changing indications for penetrating keratoplasty in Taiwan from 1987 to 1999.

PURPOSE: To determine the leading indications for penetrating keratoplasty and to identify changing trends in these indications during the past 12 years. METHODS: We retrospectively performed a chart review of the hospital records of all patients undergoing penetrating keratoplasty at the National Taiwan University Hospital during a 12-year period (1987-1999). When possible, the clinical indication was corroborated by the pathologic report. RESULTS: A total of 770 corneal transplants were performed. The leading indications for penetrating keratoplasty. in order of decreasing frequency, were corneal scars (27.9%), regraft (21.0%), acute necrotizing and ulcerative keratitis (17.9%), pseudophakic or aphakic bullous keratopathy (17.6%), Fuchs' dystrophy (4.5%), and keratoconus (2.5%). A trend of increasing frequency of regraft and acute necrotizing and ulcerative keratitis, a decreasing frequency of corneal scar, and an initially decreasing then increasing frequency of pseudophakic and aphakic bullous keratopathy were found during the 12-year study period. Acute necrotizing and ulcerative keratitis was found to be the most frequent indication for regraft. CONCLUSION: In this series, corneal scars, regraft, and acute necrotizing and ulcerative keratitis were the leading indications for penetrating keratoplasty. A changing incidence of pseudophakic and aphakic bullous keratopathy noted during the study period was related to the type of intraocular lens implanted and the method of cataract surgery performed. This study found a comparatively high frequency of acute necrotizing and ulcerative keratitis and an extremely low frequency of keratoconus compared with previous reports.

Juvenile dermatomyositis complicated with vasculitis and duodenal perforation.

Duodenal perforation has been reported in patients taking steroids and non-steroidal anti-inflammatory drugs (NSAIDs). However, its association with juvenile dermatomyositis is extremely rare. A 4-year-old boy with dermatomyositis presented with intractable abdominal pain which was aggravated after steroid and NSAID therapies. A widespread retroperitoneal abscess was noted on abdominal computerized tomography. An emergency operation showed an ulcer and perforation at the junction of the third and fourth portions of the duodenum. Debridement of the necrotic tissue and repair of the perforation were performed. The postoperative course was complicated by an anastomotic leak, which was corrected by reanastomosis. In addition to intestinal vasculitis, duodenal vasculitis complicated with ulcers and perforation should be included in the differential diagnosis of a child with juvenile dermatomyositis presenting with abdominal complaints.