Neutrophil extracellular trap production and CCL4L2 expression influence corticosteroid response in asthma.

The association between neutrophil extracellular traps (NETs) and response to inhaled corticosteroids (ICS) in asthma is unclear. To better understand this relationship, we analyzed the blood transcriptomes from children with controlled and uncontrolled asthma in the Taiwanese Consortium of Childhood Asthma Study using weighted gene coexpression network analysis and pathway enrichment methods. We identified 298 uncontrolled asthma-specific differentially expressed genes and one gene module associated with neutrophil-mediated immunity, highlighting a potential role for neutrophils in uncontrolled asthma. We also found that NET abundance was associated with nonresponse to ICS in patients. In a neutrophilic airway inflammation murine model, steroid treatment could not suppress neutrophilic inflammation and airway hyperreactivity. However, NET disruption with deoxyribonuclease I (DNase I) efficiently inhibited airway hyperreactivity and inflammation. Using neutrophil-specific transcriptomic profiles, we found that CCL4L2 was associated with ICS nonresponse in asthma, which was validated in human and murine lung tissue. CCL4L2 expression was also negatively correlated with pulmonary function change after ICS treatment. In summary, steroids fail to suppress neutrophilic airway inflammation, highlighting the potential need to use alternative therapies such as leukotriene receptor antagonists or DNase I that target the neutrophil-associated phenotype. Furthermore, these results highlight CCL4L2 as a potential therapeutic target for individuals with asthma refractory to ICS.

Mediators linking obesity to childhood asthma.

BACKGROUND: Obesity and asthma are highly associated, but the mechanisms underlying the association remain unknown. We examined five mediators linking obesity with childhood asthma: (1) pulmonary function impairment, (2) airway inflammation, (3) physical fitness, (4) sleep-disordered breathing (SDB), and (5) early puberty. METHODS: A Mendelian randomization (MR) study with mediation analysis of data obtained from 5965 children as part of the Taiwan Children Health Study. Observational analysis, MR two-stage least-squares method, and MR sensitivity analysis were carried out to investigate each causal pathway. Prospective cohort analyses were used to strengthen the findings. RESULTS: The increased asthma risk associated with obesity was found to be mostly mediated through impaired pulmonary function, low physical fitness, and early puberty. In the MR analysis, body mass index was negatively associated with FEV1/FVC and physical fitness index (ß = -2.17 and -0.71; 95% CI, -3.92 to -0.42 and -1.30 to -0.13, respectively) and positively associated with early puberty (OR, 1.09; 95% CI, 1.02-1.17). High FEV1/FVC and physical fitness index reduced asthma risk (OR, 0.98 and 0.93; 95% CI, 0.97-0.99 and 0.88-0.98, respectively), whereas SDB and early puberty increased the risk of asthma (OR, 1.03 and 1.22; 95% CI, 1.01-1.05 and 1.05-1.42, respectively). Temporal causality was strengthened in prospective cohort analyses. The three main mediators were low physical fitness, impaired pulmonary function, and early puberty, with mediation proportions of 73.76%, 61.63%, and 27.66%, respectively. CONCLUSIONS: Interventions promoting physical fitness and pulmonary function might effectively reduce obesity-induced asthma risk.

Investigating obesity-related risk factors for childhood asthma.

BACKGROUND: We tested the hypothesis that multiple obesity-related risk factors (obesity, physical activity, cardiopulmonary physical fitness, sleep-disorder breathing (SDB), and sleep quality) are associated with childhood asthma using a Mendelian randomization (MR) design. Furthermore, we aim to investigate whether these risk factors were associated with incident asthma prospectively. METHODS: In total, 7069 children aged 12 from the Taiwan Children Health Study were enrolled in the current study. Cross-sectional logistic regression, one-sample MR, summary-level MR sensitivity analyses, and prospective survival analyses were used to investigate each causal pathway. RESULTS: In MR analysis, three of the five risk factors (obesity, SDB, and sleep quality) were associated with asthma, with the highest effect sizes per inter-quartile range (IQR) increase observed for sleep quality (odds ratio [OR] = 1.42; 95% confidence interval [CI]: 1.06 to 1.92) and the lowest for obesity (OR = 1.08; 95% CI: 1.00-1.16). In the prospective survival analysis, obesity showed the highest risk of incident asthma per IQR increase (hazard ratio [HR] = 1.28; 95% CI: 1.05 to 1.56), followed by SDB (HR = 1.18; 95% CI: 1.08 to 1.29) and sleep quality (HR = 1.10; 95% CI: 1.03 to 1.17). CONCLUSION: Among the examined factors, the most plausible risk factors for asthma were obesity, SDB, and poor sleep quality. For the prevention of childhood asthma, relevant stakeholders should prioritize improving children's sleep quality and preventing obesity comorbidities such as SDB.

Effects of obesity on pulmonary function considering the transition from obstructive to restrictive pattern from childhood to young adulthood.

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Life course body mass index through childhood and young adulthood and risks of asthma and pulmonary function impairment.

BACKGROUND: Adiposity is a key risk factor for asthma and impaired pulmonary function. OBJECTIVES: We aimed to identify the critical period of life course adiposity for asthma in childhood and young adulthood, and to determine whether associations of adiposity and asthma vary across ages. METHODS: Birth weight and body mass index (BMI) from birth to 17 years of age were assessed in 6130 children from the Taiwan Children Health Study. Logistic regression for asthma outcome and linear regression for pulmonary function outcome were used to investigate associations of adiposity with asthma. Seventeen BMI-related single-nucleotide polymorphisms were used to obtain genetic instrumental variables for adiposity to perform Mendelian randomization (MR) analysis. RESULTS: Using both regression model and MR analyses, we confirmed that the critical period of adiposity in predicting childhood asthma would be before age 6 years. Further, we discovered that the sensitive period of adiposity gain related to young adulthood asthma was the prepubertal stage. Risks of asthma at age 17 per unit increase in z-score of the BMI increased from 0.94 (95% CI: 0.79-1.11) at birth, and became greater than 1.00 between age 11 and 12, then increased to 1.08 (95% CI: 0.95-1.22) at age 17. The associations of life course BMI with asthma and pulmonary function impairment at age 12 and with asthma at age 17 increased with age. The aforementioned association was most prominent among central obesity indicators. CONCLUSIONS: To prevent asthma in childhood and young adulthood, we should aim at promoting healthy growth at the toddler period and prepubertal stage.

FUT8 Remodeling of EGFR Regulates Epidermal Keratinocyte Proliferation during Psoriasis Development.

α-(1,6)-fucosyltransferase 8 (FUT8) is implicated in the pathogenesis of several malignancies, but its role in psoriasis is poorly understood. In this study, we show that FUT8 remodeling of EGFR plays a critical role in the development of psoriasis phenotypes. Notably, elevated FUT8 expression was associated with disease severity in the lesional epidermis of a patient with psoriasis. FUT8 gain of function promoted HaCaT cell proliferation, whereas short hairpin FUT8 reduced cell proliferation and induced a longer S phase with downregulation of cyclin A1 expression. Furthermore, cell proliferation, which is controlled by the activation of EGFR, was shown to be regulated by FUT8 core fucosylation of EGFR. Short hairpin FUT8 significantly reduced EGFR/protein kinase B signaling and slowed EGF‒EGFR complex trafficking to the perinuclear region. Moreover, short hairpin FUT8 reduced ligand-induced EGFR dimerization. Overactivated EGFR was observed in the lesional epidermis of both human patient and psoriasis-like mouse model, whereas conditional knockout of FUT8 in an IL-23 psoriasis-like mouse model ameliorated disease phenotypes and reduced EGFR activation in the epidermis. These findings implied that elevated FUT8 expression in the lesional epidermis is implicated in the development of psoriasis phenotypes, being required for EGFR overactivation and leading to keratinocyte hyperproliferation.

CEACAM3 decreases asthma exacerbations and modulates respiratory syncytial virus latent infection in children.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with childhood asthma. Nevertheless, not all children exposed to RSV develop asthma symptoms, possibly because genes modulate the effects of RSV on asthma exacerbations. OBJECTIVE: The purpose of this study was to identify genes that modulate the effect of RSV latent infection on asthma exacerbations. METHODS: We performed a meta-analysis to investigate differentially expressed genes (DEGs) of RSV infection from Gene Expression Omnibus datasets. Expression quantitative trait loci (eQTL) methods were applied to select single nucleotide polymorphisms (SNPs) that were associated with DEGs. Gene-based analysis was used to identify SNPs that were significantly associated with asthma exacerbations in the Taiwanese Consortium of Childhood Asthma Study (TCCAS), and validation was attempted in an independent cohort, the Childhood Asthma Management Program (CAMP). Gene-RSV interaction analyses were performed to investigate the association between the interaction of SNPs and RSV latent infection on asthma exacerbations. RESULTS: A total of 352 significant DEGs were found by meta-analysis of RSV-related genes. We used 38 123 SNPs related to DEGs to investigate the genetic main effects on asthma exacerbations. We found that eight RSV-related genes (GADD45A, GYPB, MS4A3, NFE2, RNASE3, EPB41L3, CEACAM6 and CEACAM3) were significantly associated with asthma exacerbations in TCCAS and also validated in CAMP. In TCCAS, rs7251960 (CEACAM3) significantly modulated the effect of RSV latent infection on asthma exacerbations (false-discovery rate <0.05). The rs7251960 variant was associated with CEACAM3 mRNA expression in lung tissue (p for trend=1.2×10-7). CEACAM3 mRNA was reduced in nasal mucosa from subjects with asthma exacerbations in two independent datasets. CONCLUSIONS: rs7251960 is an eQTL for CEACAM3, and CEACAM3 mRNA expression is reduced in subjects experiencing asthma exacerbations. CEACAM3 may be a modulator of RSV latent infection on asthma exacerbations.

Early pubertal maturation and risk of childhood asthma: A Mendelian randomization and longitudinal study.

BACKGROUND: Studies on early puberty and incident asthma have reported inconsistent results and are mainly performed in females. In this longitudinal study, we investigated the causal relationship between pubertal maturation and asthma through Mendelian randomization (MR) and explored the joint effect of overweightness and early pubertal maturation on asthma. METHODS: We used data from the Taiwan Children Health Study with longitudinal follow-ups of 2991 children aged 11-17 years. Six puberty-related single-nucleotide polymorphisms (combined into a weighted allelic score) were used to yield genetic instrumental variables for early puberty. Early pubertal maturation was defined as reaching a certain pubertal stage earlier than the median age for that stage. Incident asthma cases were calculated by excluding children with a history of asthma prior to that age. RESULTS: The results of MR analysis revealed that early pubertal maturation was associated with active asthma (OR = 1.18; 95% CI: 1.08-1.28); this effect was significant in male children. Early pubertal maturation significantly increased the risk of incident asthma outcomes at 12 and 17 years of age in both sexes (hazard ratio = 2.15; 95% CI: 1.21-3.84). Taking non-overweight and non-early puberty children as the reference group, we observed a synergistic effect of overweightness and early pubertal maturation on asthma risk (OR = 1.08; 95% CI: 1.04-1.11) in children of both sexes. CONCLUSIONS: Early screening and intervention for obesity are recommended to prevent future early pubertal onset and asthma occurrence.

Body mass index growth trajectories, early pubertal maturation, and short stature.

BACKGROUND: Childhood body mass index (BMI) trajectory classes are rarely linked to early puberty risk, particularly among Chinese children. We estimated early puberty risk across BMI trajectory classes, investigated factors contributing to pubertal development, and examined differences in final adult height between children exhibiting early and nonearly pubertal maturation across the classes. METHODS: The Taiwan Children Health Study recruited 10-year-old children in 2010 from 14 Taiwanese communities and resurveyed them at age 11, 12, and 18 years. The study comprised 3109 children (50.4% boys) with available data for BMI (age 6-11 years) and pubertal stages (age 11, 12, and 18 years). RESULTS: Classes 1-4 were persistently healthy weight, rapid BMI growth, chronically overweight/obese, and early transient overweight/obese. Children in class 3 exhibited the highest risk of early pubertal maturation. Puberty genetic score, low sleep quality, and high fat-free mass collectively explained 15% of the variance in Tanner stages among class 3 children. Early pubertal maturation was considered to cause short and tall stature in boys and girls, respectively. CONCLUSIONS: Modifying sleep quality and fat-free mass may reduce early puberty risk in children with chronic overweight/obesity. Vigorous physical activity may reduce adiposity and increase the final adult height in the children.

Trends and Age-Period-Cohort Effects of Fertility Rate: Analysis of 26,224 Married Women in Taiwan.

Taiwan and a few Asian societies have had among the lowest fertility rates in the world for the past decade. Understanding the reasons behind the low fertility and designing policies accordingly to improve fertility has been a priority of governments in the region. It what follows we examine the low fertility rate in Taiwan by studying the trend of actual fertility rate and desired fertility rate in Taiwan using an age-period-cohort (APC) model. Using the Knowledge, Attitude, and Practice (KAP) of contraception survey data between 1973 and 2004, we applied APC analyses on the actual fertility rate and desired fertility rate of married women. We found that youngest cohorts (the mid-cohort year 1983) had 10% higher actual fertility and 15% higher desired fertility compared to those who were born in 1959-1965, respectively. Additionally, we attributed current lowest-low fertility (at or below 1.3) to late marriages. There is a lag between the actual and desired fertility rates in KAP survey due to tempo effect. Furthermore, the trends of the cohort effects of both fertility rates in KAP surveys are reversing in Taiwan. Consequently, increase total fertility rate (TFR) should encourage marriage among the marriageable population and reward married and childbearing households.

Assessing causality between childhood adiposity and early puberty: A bidirectional Mendelian randomization and longitudinal study.

AIMS: Obesity and early puberty have been reported to be mutually causative. We investigated the causal relationship between adiposity and early puberty by performing bidirectional Mendelian randomization (MR) and longitudinal data analyses. METHODS: We used information from the Taiwan Children Health Study (3109 adolescents aged 11-12 years) with 17 body mass index (BMI)- and 10 puberty-related single-nucleotide polymorphisms (SNPs) to produce genetic instrumental variables (IVs). The two-stage least squares (2SLS) method, MR sensitivity analysis, and survival analysis were used to explore and confirm causality. RESULTS: Regression estimates from IVs revealed that significantly increased association of BMI with early puberty was noted (coefficients: 0.13, 0.10, and 0.09; 95% CI: 0.07-0.19, 0.02-0.19, and 0.02-0.16 for all participants, male adolescents, and female adolescents, respectively). Genetic IVs for puberty were not associated with BMI. MR sensitivity and two-sample MR analyses produced similar results. Longitudinal analysis results revealed that prepubertal overweight and obesity could predict early onset of puberty. However, after excluding children with a history of overweight and obesity at the age of 7-12 years, early puberty was not found to trigger new-onset of overweight and obesity at the age of 18 years in either sex. CONCLUSIONS: Higher adiposity may lead to early puberty. However, the causal effects of early puberty on adiposity accumulation were not supported by our data. Targeted interventions to reduce childhood obesity are strongly recommended to prevent obesity-related comorbidities, as well as early puberty onset.

Causal relationships between adiposity and childhood asthma: bi-directional Mendelian Randomization analysis.

BACKGROUND/OBJECTIVES: Obesity and asthma are common chronic diseases and have been reported to be mutually causative. We investigated the causal direction of the relationship between adiposity and asthma using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. SUBJECTS/METHODS: We used data from the Taiwan Children Health Study with 24 body mass index (BMI)-single-nucleotide polymorphisms (SNPs, combined into a weighted allelic score) and 16 asthma-SNPs (combined into two weighted allelic scores, separately for asthma inflammatory and antioxidative genes) to yield genetic IVs for adiposity and asthma, respectively. RESULTS: The weighted allele score for BMI was strongly associated with adiposity (p = 2 × 10-16) and active asthma (p = 0.03). The two-stage least square regression risk ratio (RR) for the effect of BMI on asthma was 1.04 (95% confidence interval: 1.00-1.07, p = 0.03). Although the weighted asthma genetic scores were significantly associated with asthma (p = 8.4 × 10-3), no association was seen for genetically instrumented asthma with BMI using MR. Central obesity was the most accurate predictor of asthma. Adiposity showed higher causal effects on asthma in boys and children with non-atopic asthma. Sensitivity analysis for MR revealed no directional genetic pleiotropy effects. The causal effect RRs of BMI on asthma were 1.04, 1.08, and 1.03 for inverse-variance weighted, MR-Egger regression (slope), and weighted median methods, respectively, all in accordance with the MR estimates. CONCLUSIONS: High adiposity may lead to asthma, whereas the effects of asthma on adiposity accumulation are likely to be small.

Birthweight, time-varying adiposity growth and early menarche in girls: A Mendelian randomisation and mediation analysis.

OBJECTIVE: To explore the causal effect of time-varying z-BMI growth on early menarche using Mendelian randomisation (MR); to identify critical adiposity predictors of early menarche; to compare the effects of birthweight and time-varying z-BMI growth as mediators of the path from genes to early menarche using mediation analysis. METHODS: We used data from the Taiwan Children Health Study with 21 obesity-related single-nucleotide polymorphisms (SNPs) to yield genetic (instrumental variable)IVs for adiposity. Children with available data on genotyping, birthweight, adiposity, and menarcheal age were included. RESULTS: In MR analyses, results based on the time-varying z-BMI growth show more statistical power and capture more information of adiposity growth (p=0.01) than those based on single point z-BMI (p=0.02). Among adiposity measures, critical predictors of early menarche are fat free mass (RR=1.33, 95% CI 1.07-1.65) and waist/height ratio (RR=1.27, 95% CI 1.03-1.56). Other potential predictors of early menarche are sum of skinfold (RR=1.24, 95% CI 1.03-1.48) and total body fat (RR=1.20, 95% CI 1.05-1.38). In both one-mediation and multi-mediation analyses, time-varying z-BMI growth in the prepubertal years plays a crucial mediator in the pathway from the genes to early menarche. CONCLUSIONS: This study discovered that greater prepubertal adiposity growth is a crucial mediator in the path from genes to early menarche. For girls with genes positively associated with obesity; and/or of lower birthweight, a strategy to prevent childhood adiposity should be implemented in order to avoid early menarche development.

A simple prediction tool for inhaled corticosteroid response in asthmatic children.

BACKGROUND: Inhaled corticosteroids are recommended as the first-line controller medication for childhood asthma owing to their multiple clinical benefits. However, heterogeneity in the response towards these drugs remains a significant clinical problem. METHODS: Children aged 5 to 18 years with mild to moderate persistent asthma were recruited into the Taiwanese Consortium of Childhood Asthma Study. Their responses to inhaled corticosteroids were assessed based on their improvements in the asthma control test and peak expiratory flow. The predictors of responsiveness were demographic and clinical features that were available in primary care settings. We have developed a prediction model using logistic regression and have simplified it to formulate a practical tool. We assessed its predictive performance using the area under the receiver operating characteristic curve. RESULTS: Of the 73 asthmatic children with baseline and follow-up outcome measurements for inhaled corticosteroids treatment, 24 (33%) were defined as non-responders. The tool we have developed consisted of three predictors yielding a total score between 0 and 5, which are comprised of the following parameters: the age at physician-diagnosis of asthma, sex, and exhaled nitric oxide. Sensitivity and specificity of the tool for prediction of inhaled corticosteroids non-responsiveness, for a score of 3, were 0.75 and 0.69, respectively. The areas under the receiver operating characteristic curve for the prediction tool was 0.763. CONCLUSIONS: Our prediction tool represents a simple and low-cost method for predicting the response of inhaled corticosteroids treatment in asthmatic children.

Obesity and the occurrence of bronchitis in adolescents.

OBJECTIVE: Previous studies have shown that an elevated BMI was associated with higher risks of bronchitis among children. The magnitude of how increase in BMI influencing the risk of incident bronchitis remained unexplored. The objective of this study is to assess the association between BMI and the incidence of bronchitis in the Taiwan Children Health Study. DESIGN: A school-based prospective cohort study. METHODS: We conducted a population-based prospective cohort study among seventh-grade school children in 14 Taiwanese communities. A total of 3,634 adolescents completed follow-up questionnaire in 2009. Associations between BMI and incident bronchitis were analyzed by multiple Poisson regression models, taking overdispersion into account. RESULTS: Among eligible cohort participants without bronchitis at study entry, the proportion of overweight and obesity were 32.1% and 17.9%. Overweight was 40.7% and obesity was 27.7% among those with incident bronchitis. The BMI percentile categories showed significant increasing trends for bronchitis in total eligible children and in girls (P for trend <0.001). Overweight and obesity were both associated with increased risks of incident bronchitis. This association was significant in girls only while stratified by gender. CONCLUSIONS: Our data showed that the BMI percentile and weight status were associated with higher risks of incident bronchitis in adolescents, especially in girls.

Home dampness, beta-2 adrenergic receptor genetic polymorphisms, and asthma phenotypes in children.

BACKGROUND: Dampness in the home is a strong risk factor for respiratory symptoms and constitutes a significant public health issue in subtropical areas. However, little is known about the effects of dampness and genetic polymorphisms on asthma. METHODS: In 2007, 6078 schoolchildren were evaluated using a standard questionnaire with regard to information about respiratory symptoms and environmental exposure. Multiple logistic regression analyses were performed to assess the effects of home dampness and beta-2-adrenergic receptor (ADRB2) gene polymorphisms on the prevalence of asthma and selected indicators of severity of asthma. RESULTS: The frequency of mildewy odor, the number of walls with water stamp, and the duration of water damage were all associated with being awakened at night due to wheezing. However, no other clear-cut associations were found for any of the other indicators of asthma. Children exposed to mildewy odor with ADRB2 Arg/Arg genotype were associated with being awakened at night due to wheezing (OR=1.95, 95% CI, 1.14-3.36), compared to those without exposure and with the ADRB2 Gly allele. ADRB2 Arg16Gly showed a significant interactive effect with home dampness on being awakened at night due to wheezing and current wheezing, but no significant effect on active asthma and medication use. Frequency and degree of home dampness were also associated with the prevalence of asthma and selected indicators of severity of asthma, in an exposure-response manner among children with ADRB2 Arg/Arg genotype. CONCLUSIONS: Home dampness prevention is one of the important steps of asthma control, especially in children carrying ADRB2 Arg/Arg genotypes.

Prevalence, awareness, treatment, control, and risk factors associated with hypertension in urban adults from 33 communities of China: the CHPSNE study.

OBJECTIVE: To assess the prevalence, awareness, treatment, and control of hypertension and their associated factors in an urban Chinese population. METHODS: A cross-sectional study was conducted in three cities in northeast China from 2009 to 2010, using a multistage cluster sampling method to select a representative sample. A total of 25 196 adults, aged 18-74 years, were examined in 33 communities. Hypertension was defined as a mean SBP of at least 140 mmHg, DBP at least 90 mmHg, and/or use of antihypertensive medications. RESULTS: Overall, the prevalence of hypertension was 28.7% for urban residents, and 39.1% for middle-aged and elderly residents (aged ≥35 years). Among all the hypertensive patients examined in the study (n = 7237), 42.9% were aware of their condition, 28.2% were receiving treatment, and only 3.7% had their blood pressure adequately controlled. Female hypertensive patients had more effectively controlled blood pressure than their male counterparts. Among the study participants, 37.9% did not think that high blood pressure would endanger their lives. Among hypertensive patients aware of their conditions, the primary reason for not taking antihypertensive medication was a lack of money (34.8%). Age, sex, education, occupation, income, body mass, waist circumference, and family hypertension history significantly correlated with the prevalence of hypertension. CONCLUSION: Hypertension is highly prevalent in the urban population of China, and the effects of being overweight/obesity on hypertension were much larger than any other examined factors. The percentage of hypertensive patients aware of their condition, receiving proper treatment, and keeping their hypertension under control is unacceptably low.

Tumour necrosis factor G-308A polymorphism modifies the effect of home dampness on childhood asthma.

OBJECTIVES: Environmental exposure at home, such as dampness, has been shown to have adverse effects on respiratory health. However, few studies explored the association between home dampness and genetic polymorphisms on childhood asthma. The aim of the study is to evaluate the effects of home dampness and tumour necrosis factor-α gene (TNF-α) on asthma in Taiwanese children. METHODS: The authors investigated 3810 schoolchildren in Taiwan Children Health Study from 14 communities. Children's exposure and disease status were measured from a parental questionnaire. Multiple logistic regression models were fitted to estimate the effects of home dampness exposure and TNF-α genotypes on the prevalence of asthma and wheeze. RESULTS: Mildewy odour at home was significantly associated with increased prevalence of lifetime wheeze (OR=1.36, 95% CI 1.05 to 1.77, p for trend=0.04). The effects of water stamp on the wall at home were associated with lifetime asthma and lifetime wheeze. Children with water stamp on the wall at home and TNF-308 A allele had increased risks on lifetime asthma, active asthma and lifetime wheeze. TNF-α showed significant interactive effects with mildewy odour on lifetime asthma (p for interaction=0.01), and with water stamp on the wall at home on lifetime wheeze (p for interaction=0.04). Under stratification by TNF-308 genotypes, we found that the frequency of water stamp on the wall was associated with increased risks of all asthma subcategories and lifetime wheeze among TNF-308 GA or AA genotypes (p for trend<0.05). CONCLUSIONS: Home dampness is a risk factor for asthma and wheeze among children, especially for those with the TNF-308 A allele.

Association between the initial anatomical severity and opportunity of return to work in occupational hand injured patients.

BACKGROUND: The severity of the injury is the most important factor to return to work (RTW) when it comes to hand injuries. The purpose of our study is to examine the relationship between the initial anatomic severity, evaluated by the Hand Injury Severity Scoring (HISS) system, and probability of RTW in occupational hand injured patients. METHODS: In this retrospective cohort study, 140 patients hospitalized for surgery due to occupational hand injuries between 2004 and 2008 were recruited. Participants were interviewed for occupational history and RTW status. The probability of RTW was compared with the initial HISS scores by multiple logistic regression models. RESULTS: In workers' compensation group, there was a significant relationship between HISS severity and the probability of RTW. Compensated patients with moderate injuries (odds ratio [OR] = 0.15; 95% confidence interval [CI], 0.03-0.70) and severe injuries (OR = 0.13; 95% CI, 0.02-0.75) were significantly less likely to RTW than those with minor injuries, and those with major injuries were the least likely to RTW (OR = 0.07; 95% CI, 0.01-0.36). However, no association was found between HISS severity and the probability of RTW for patients without workers' compensation. With regard to the HISS components, patients with motor or neural component deficits had a significantly lower opportunity of RTW, with the neural deficits being the most influential. CONCLUSION: HISS is a useful instrument to predict the opportunity of RTW while restricted to the compensated patients. We also verified that the relationship between HISS severity and the probability of RTW existed for groups but not for individual patients.