Restraint Stress-Induced Neutrophil Inflammation Contributes to Concurrent Gastrointestinal Injury in Mice.

Psychological stress increases risk of gastrointestinal tract diseases. However, the mechanism behind stress-induced gastrointestinal injury is not well understood. The objective of our study is to elucidate the putative mechanism of stress-induced gastrointestinal injury and develop an intervention strategy. To achieve this, we employed the restraint stress mouse model, a well-established method to study the pathophysiological changes associated with psychological stress in mice. By orally administering gut-nonabsorbable Evans blue dye and monitoring its plasma levels, we were able to track the progression of gastrointestinal injury in live mice. Additionally, flow cytometry was utilized to assess the viability, death, and inflammatory status of splenic leukocytes, providing insights into the stress-induced impact on the innate immune system associated with stress-induced gastrointestinal injury. Our findings reveal that neutrophils represent the primary innate immune leukocyte lineage responsible for stress-induced inflammation. Splenic neutrophils exhibited elevated expression levels of the pro-inflammatory cytokine IL-1, cellular reactive oxygen species, mitochondrial burden, and cell death following stress challenge compared to other innate immune cells such as macrophages, monocytes, and dendritic cells. Regulated cell death analysis indicated that NETosis is the predominant stress-induced cell death response among other analyzed regulated cell death pathways. NETosis culminates in the formation and release of neutrophil extracellular traps, which play a crucial role in modulating inflammation by binding to pathogens. Treatment with the NETosis inhibitor GSK484 rescued stress-induced neutrophil extracellular trap release and gastrointestinal injury, highlighting the involvement of neutrophil extracellular traps in stress-induced gastrointestinal inflammation. Our results suggest that neutrophil NETosis could serve as a promising drug target for managing psychological stress-induced gastrointestinal injuries.

Pulmonary IL-33 orchestrates innate immune cells to mediate respiratory syncytial virus-evoked airway hyperreactivity and eosinophilia.

BACKGROUND: Respiratory syncytial virus (RSV) infection is epidemiologically linked to asthma. During RSV infection, IL-33 is elevated and promotes immune cell activation, leading to the development of asthma. However, which immune cells are responsible for triggering airway hyperreactivity (AHR), inflammation and eosinophilia remained to be clarified. We aimed to elucidate the individual roles of IL-33-activated innate immune cells, including ILC2s and ST2+ myeloid cells, in RSV infection-triggered pathophysiology. METHODS: The role of IL-33/ILC2 axis in RSV-induced AHR inflammation and eosinophilia were evaluated in the IL-33-deficient and YetCre-13 Rosa-DTA mice. Myeloid-specific, IL-33-deficient or ST2-deficient mice were employed to examine the role of IL-33 and ST2 signaling in myeloid cells. RESULTS: We found that IL-33-activated ILC2s were crucial for the development of AHR and airway inflammation, during RSV infection. ILC2-derived IL-13 was sufficient for RSV-driven AHR, since reconstitution of wild-type ILC2 rescued RSV-driven AHR in IL-13-deficient mice. Meanwhile, myeloid cell-derived IL-33 was required for airway inflammation, ST2+ myeloid cells contributed to exacerbation of airway inflammation, suggesting the importance of IL-33 signaling in these cells. Local and peripheral eosinophilia is linked to both ILC2 and myeloid IL-33 signaling. CONCLUSIONS: This study highlights the importance of IL-33-activated ILC2s in mediating RSV-triggered AHR and eosinophilia. In addition, IL-33 signaling in myeloid cells is crucial for airway inflammation.

Sex-moderated interactions between IL4/IL13 pathway genes and prenatal environment on cord blood IgE levels.

BACKGROUND: Elevated cord blood IgE (cIgE), a predictor of atopic diseases, is influenced by genetic and environmental factors. However, gene-environment interactions on cIgE elevation and their difference by sex remain largely unexplored. OBJECTIVE: This study aimed to determine whether there are sex-moderated interactions between genetic variants in the IL4/IL13 pathway and prenatal environments on cIgE elevation. METHODS: Comprehensive information on environmental tobacco smoke (ETS), home dampness (indexed by combining mildewy odour, visible mould and water stamp on the wall) and other household environments was obtained using a structured questionnaire during the third trimester of pregnancy in 1107 full-term newborns. The cord blood was collected for measuring cIgE levels, with elevation defined as ≥0.5 IU/mL, and for genotyping of five single nucleotide polymorphisms of three candidate genes (IL-13 rs1800925, rs20541, rs848, IL-4 rs2243250 and STAT6 rs324011). RESULTS: Gene-environment interactions on cIgE elevation were observed in male but not female newborns, including those between ETS and IL13 rs20541, between home dampness and STAT6 rs324011, and between composite environmental exposure (combined ETS and the three home dampness indices) and STAT6 rs324011 (P for interaction = 0.03, 0.006, and 0.001, respectively). Male newborns carrying STAT6 rs324011 CT or TT genotype manifested with a significant dose-response association of the composite environmental exposure with cIgE elevation. CONCLUSION AND CLINICAL RELEVANCE: Sex moderates the gene-environment interactions involving IL4/IL13 pathway genes and prenatal household environments on cIgE elevation. The absence of prenatal exposure to ETS and home dampness in male neonates carrying the STAT6 rs324011 CT or TT genotype is least likely associated with cIgE elevation.

Growth trajectories and asthma/rhinitis in children: a longitudinal study in Taiwan.

Studies have reported the effect of body weight in early childhood on asthma. However, the effect of growth patterns during school age on asthma and rhinitis has yet to be explored. We sought to investigate whether various growth patterns predict incident asthma and rhinitis.We conducted a nationwide longitudinal study (Taiwan Children Health Study) in 14 Taiwanese communities. Body mass index (BMI) z-scores of 4422 children aged 6-11 years were collected annually and distinct growth trajectory classes were identified using a latent generalised mixture model. Pulmonary function and exhaled nitric oxide fraction (FeNO) levels were also measured. Whether different growth trajectory classes predict incident asthma and rhinitis at age 12, 15 and 18 years was determined using a discrete time hazard model.Four growth trajectory classes were identified. Persistently overweight children exhibited significantly increased risks of asthma and rhinitis at age 12 years. Furthermore, being persistently overweight had a long-term effect on incident asthma (hazard ratio 2.47, 95% CI 1.18-5.12) and rhinitis (hazard ratio 1.44, 95% CI 1.12-1.84) in adolescence and early adulthood. Children in high BMI classes exhibited significantly lower pulmonary functions compared with normal growth children. FeNO levels were lower in children in the high BMI classes and higher in children showing declining obesity compared with normal growth children.Persistently overweight children exhibited incident asthma and rhinitis in adolescence and early adulthood.

Newborn genetic screening for hearing impairment: a population-based longitudinal study.

PURPOSE: The feasibility of genetic screening for deafness-causing mutations in newborns has been reported in several studies. The aim of this study was to investigate the long-term results in those who screened positive for deafness mutations; these results are crucial to determine the cost-effectiveness to justify population-wide genetic screening. METHODS: We performed simultaneous hearing screening and genetic screening targeting four common deafness mutations (p.V37I and c.235delC of GJB2, c.919-2A>G of SLC26A4, and the mitochondrial m.1555A>G) in 5173 newborns at a tertiary hospital between 2009 and 2015. Serial audiometric results up to 6 years old were then analyzed in children with conclusive genotypes. RESULTS: Newborn genetic screening identified 82 (1.6%) babies with conclusive genotypes, comprising 62 (1.2%) with GJB2 p.V37I/p.V37I, 16 (0.3%) with GJB2 p.V37I/c.235delC, and 4 (0.1%) with m.1555A>G. Of these, 46 (56.1%) passed hearing screening at birth. Long-term follow-up demonstrated progressive hearing loss in children with the GJB2 p.V37I/p.V37I and p.V37I/c.235delC genotypes; this hearing loss deteriorated by approximately 1 decibel hearing level (dBHL) per year. CONCLUSIONS: We delineated the longitudinal auditory features of the highly prevalent GJB2 p.V37I mutation on a general population basis and confirmed the utility of newborn genetic screening in identifying infants with late-onset or progressive hearing impairment undetectable by newborn hearing screening.Genet Med 19 1, 6-12.

Perfluoroalkyl substance exposure and urine CC16 levels among asthmatics: A case-control study of children.

BACKGROUND: Studies have reported an association between serum perfluoroalkyl substances (PFASs) and asthma. However, few studies have examined the possible associations between PFASs and the 16-kDa club cell secretory protein (Clara) (CC16) level, a prominent biomarker of asthma, among adolescents. METHODS: We recruited a total of 231 asthmatic children and 225 non-asthmatic controls in the Genetic and Biomarkers study for Childhood Asthma (GBCA) in northern Taiwan from 2009 to 2010. Structured questionnaires were administered by face-to-face interview. Urine CC16 was determined by an enzyme-link immunoassay kit. Multiple general linear models were employed to examine the associations between PFASs and urinary CC16 levels. RESULTS: Asthmatic participants had significantly higher serum PFAS concentrations overall than the healthy controls. After adjusting for confounding factors, urinary CC16 was significantly, negatively associated with PFASs, especially PFOS, PFOA, PFDA and PFNA, and especially among males, as follows: PFOS (ß = -0.003, 95% confidence interval [CI]: -0.004, -0.002), PFOA (ß = -0.045, 95% CI: -0.086, -0.004), and PFHxA (ß = -0.310, 95% CI: -0.455, -0.165) among asthmatic boys, and PFDA (ß = -0.126, 95%CI: -0.241, -0.012) and PFNA (ß = -0.329, 95% CI: -0.526, -0.132) among non-asthmatic boys. Among girls, PFDA (ß = -0.088, 95% CI: -0.172, -0.004), was the only PFAS significantly associated with CC16. Significant interaction effects (p < 0.15) on CC16 levels were found between asthma and PFOS, PFOA, PFBS and PFHxA in all participants. CONCLUSION: Our overall results showed that serum PFASs were significantly, inversely associated with CC16 levels. Associations were stronger among males.

Association of perfluoroalkyl substances exposure with impaired lung function in children.

Previous studies have demonstrated associations between serum levels of perfluoroalkyl substances (PFASs) and asthma or asthma related-biomarkers. However, no studies have reported a possible relationship between PFASs exposure and lung function among children. The objective of the present study is to test the association between PFASs exposure and lung function in children from a high exposure area by using a cross-sectional case-control study, which included 132 asthmatic children and 168 non-asthmatic controls recruited from 2009 to 2010 in the Genetic and Biomarkers study for Childhood Asthma. Structured questionnaires were administered face-to-face. Lung function was measured by spirometry. Linear regression models were used to examine the influence of PFASs on lung function. The results showed that asthmatics in our study had significantly higher serum PFAS concentrations than healthy controls. Logistic regression models showed a positive association between PFASs and asthma, with adjusted odds ratios (ORs) ranging from 0.99 (95% confidence interval [CI]: 0.80-1.21) to 2.76 (95% CI: 1.82-4.17). Linear regression modeling showed serum PFASs levels were significantly negatively associated with three pulmonary function measurements (forced vital capacity: FVC; forced expiratory volume in 1s: FEV1; forced expiratory flow 25-75%: FEF25-75) among children with asthma, the adjusted coefficients between lung function and PFASs exposure ranged from -0.055 (95%CI: -0.100 to -0.010) for FVC and perfluorooctane sulfonate (PFOS) to -0.223 (95%CI: -0.400 to -0.045) for FEF25-75 and perfluorooctanoic acid (PFOA). PFASs were not, however, significantly associated with pulmonary function among children without asthma. In conclusion, this study suggests that serum PFASs are associated with decreased lung function among children with asthma.

Mediating pathways from central obesity to childhood asthma: a population-based longitudinal study.

The mediating pathways linking obesity and asthma are largely unknown. We aimed to investigate the mediating pathways and to search for the most prominent pathological mechanism between central obesity and childhood asthma.In the Taiwan Children Health Study, we collected data on an open cohort of children aged 9-13 years. Children's respiratory outcomes, atopic conditions, obesity measures and pulmonary function were surveyed annually between 2010 and 2012. Exhaled nitric oxide fraction concentrations were recorded in 2012. Generalised estimating equations and general linear models were used to examine the associations between central obesity, possible mediators and asthma. Structural equation models were applied to investigate the pathways that mediate the link between central obesity and asthma.Central obesity (waist-to-hip ratio) most accurately predicted childhood asthma. In the active asthma model, the percentage of mediation was 28.6% for pulmonary function, 18.1% for atopy and 5.7% for airway inflammation. The percentage of mediation for pulmonary function was 40.2% in the lifetime wheeze model. Pulmonary function was responsible for the greatest percentage of mediation among the three mediators in both models.Decline in pulmonary function is the most important pathway in central obesity related asthma. Pulmonary function screening should be applied to obese children for asthma risk prediction.

Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells.

Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke.

Associations between allergic diseases and attention deficit hyperactivity/oppositional defiant disorders in children.

BACKGROUND: We aim to investigate the detailed associations between allergic diseases with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among children. METHODS: Clinical information from 2,896 children enrolled in the Taiwan Children Health Study was obtained for analyses. Allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis, have been evaluated based on the questions adjusted from International Study of Asthma and Allergies in Childhood. The Swanson, Nolan, and Pelham questionnaire was used to assess symptoms of ADHD and ODD. Symptoms of depression, stress, and poor sleep quality were evaluated as the interactive risk factors. RESULTS: Children having symptoms of allergic diseases within the past 1 y were associated with having all dimensions of symptoms of ADHD and ODD. Children with ever having a physician-diagnosed atopic dermatitis were associated with inattentive and hyperactive-impulsive symptoms of ADHD. Ever diagnosed asthma was associated with ADHD and ODD. Ever diagnosed allergic rhinitis was associated with inattentive and combined symptoms of ADHD and ODD. CONCLUSION: Children with allergic diseases, such as atopic dermatitis, asthma, and allergic rhinitis, were associated with exhibiting ADHD and ODD.

Associations between Respiratory Diseases and Dietary Patterns Derived by Factor Analysis and Reduced Rank Regression.

BACKGROUND/AIMS: The study aims to identify children's dietary patterns and explore the relationship between dietary patterns and respiratory diseases. METHODS: Subjects were 2,397 fourth graders in 14 Taiwanese communities who participated in the Taiwan Children Health Study. This study is based on an evaluation of dietary patterns, performed from April until June 2011. Information pertaining to respiratory disease was obtained by The International Study of Asthma and Allergies in Childhood questionnaire, and dietary intake data obtained by food frequency questionnaire. Factor analysis and reduced rank regression (RRR) were both used to analyze dietary patterns. RESULTS: Using factor analysis, it was found that children on a high-protein, high-fat, Western diet had a significantly higher risk of allergic rhinitis (OR 1.10, 95% CI 1.01-1.20). Lower ORs were noted for current wheezing, ever asthma and bronchitis in children eating a healthy diet than those on a high-protein, high-fat, Western diet. Using RRR, it was found that children on a high-protein, high-fat diet had significantly higher risks of allergic rhinitis (OR 1.17, 95% CI 1.07-1.27), current wheezing (OR 1.23, 95% CI 1.04-1.45) and bronchitis (OR 1.26, 95% CI 1.09-1.46). CONCLUSIONS: A diet rich in fat and protein may increase the risk of respiratory disease in children.

Age of asthma onset and vulnerability to ambient air pollution: an observational population-based study of adults from Southern Taiwan.

BACKGROUND: Late-onset asthma (onset > 12 years) is pathologically distinct from early-onset asthma. The mechanism of air pollution is not a classic allergic inflammation and could have differential effect on late-onset and early-onset asthma. However, there is little known about the association of onset-age phenotype and air pollution. In this population-based study, we aimed to determine the association of asthma severity outcomes and air pollution regarding age at onset of asthma. METHODS: In 2004, we conducted a cross-sectional questionnaire survey about respiratory health among schoolchildren's parents randomly selected from 94 of 816 elementary and middle schools in southern Taiwan. Participants ever having typical asthma symptoms were enrolled. We used kriging method to estimate individual exposure to ambient air pollution in the preceding year before the year of asthma severity survey. Ordered logistic regression was used to determine the association of exposure and asthma severity scores. Age at asthma onset of 12 years was used as a cut-off to define early- or late-onset asthma. RESULTS: The study surveyed 35,682 participants. Data from 23,551 participants remained satisfactory with a response rate of 66 %. Among 20,508 participants aged 26-50 years, 703 questionnaire-determined asthmatics were identified and included for analysis. Using the median of PM10 (66 µg/m(3)) as a cut-off, those exposed to higher PM10 were more likely to have higher severity scores (OR = 1.74; 95 % CI, 1.13 - 2.70) only for asthmatics with asthma onset at > 12 years. CONCLUSIONS: In adulthood, exposure to PM10 has a greater effect on late-onset asthma than early-onset asthma and deserves greater attention among ambient air pollutants.

Associations between ozone and preterm birth in women who develop gestational diabetes.

Prenatal exposure to ambient air pollutants might cause adverse birth outcomes; however, there have been few studies in which the association between air pollution and preterm birth was examined after stratifying by pregnancy complications. We conducted a population-based case-control study of 1,510,064 singleton births from the Taiwanese birth registry during 2001-2007. Of the total of 1,510,064 births, we designated all 86,224 preterm births as the case group and then randomly selected an additional 344,896 from the remaining births (equivalent to 4 full-term births for every 1 preterm birth) as the control sample. We used an inverse distance weighting approach to calculate an average exposure parameter for air pollutants. The adjusted odds ratio for preterm birth per 10-ppb increase in ozone was 1.12 (95% confidence interval: 1.01, 1.23) for women with gestational diabetes mellitus who were exposed in the third trimester and 1.02 (95% confidence interval: 1.01, 1.03) for women without gestational diabetes (P for interaction <0.001). These findings suggest that exposure to ozone in pregnancy is associated with an increased risk of preterm birth, particularly for women who have gestational diabetes mellitus.

Different Severity and Severity Predictors in Early-Onset and Late-Onset Asthma: A Taiwanese Population-Based Study.

BACKGROUND: Late-onset asthma has been shown to be more severe than early-onset asthma in clinic-based studies. However, population-based studies are scarce, and the predictors of severity have been less studied. OBJECTIVES: To determine asthma severity and severity predictors regarding age at onset. METHODS: A cross-sectional questionnaire survey was conducted among parents of children from 94 schools in Taiwan in 2004. Asthma severity was defined as short-acting ß2-agonist (SABA), inhaled corticosteroid (ICS) and health care use in the last year. Information on age at onset, demographics, heredity and home exposure was collected. Ordered logistic or logistic regression was used for determining the associations between risk factors and severity. RESULTS: Participants aged 26-50 years were included, resulting in 21,057 (67.8%) participants. Among them, 449 reported ever having had physician-diagnosed asthma, and 381 of those subjects answered the question on age at asthma onset. The risks of rescue SABA, ICS and health care use were generally higher among late-onset (13-50 years) than early-onset (0-12 years) asthmatics. Use of SABA and health care increased from childhood-onset, adolescent- or young adult-onset to adult-onset asthma. Allergic rhinitis was positively associated with SABA use (OR, 9.08; 95% CI, 1.06-77.99) and ICS use (OR, 5.08; 95% CI, 1.47-17.52) in early-onset asthma. Dehumidifier use was negatively associated with SABA use (OR, 0.50; 95% CI, 0.29-0.87) and ICS use (OR, 0.38; 95% CI, 0.19-0.78) in late-onset asthma. CONCLUSIONS: In adults, late-onset asthma was more severe than early-onset asthma. Severity, as indicated by SABA and ICS use, was positively associated with allergic rhinitis in early-onset asthma and negatively associated with dehumidifier use in late-onset asthma.

Pathway from central obesity to childhood asthma. Physical fitness and sedentary time are leading factors.

RATIONALE: Available prospective studies of obesity and asthma have used only body mass index (BMI) as an indicator for adiposity; studies using detailed obesity measures are lacking, and the role of physical fitness level and sedentary time remains unexplored in the link between obesity and asthma. OBJECTIVES: To compare various anthropometric measures of obesity in relation to childhood asthma, and to further characterize the interrelations among central obesity, physical fitness level, sedentary time, and asthma. METHODS: The nationwide Taiwan Children Health Study followed 2,758 schoolchildren from fourth to sixth grade, annually collecting data regarding physical fitness, sedentary time, obesity measures (comprising body weight and height, abdominal and hip circumference, skin fold thickness, and body composition), asthma, and pulmonary function tests. The generalized estimating equation was used for 3 years of repeated measurements to analyze the interrelation among obesity, sedentary time, physical fitness level, and asthma; a structural equation model was used to explore the pathogenesis among these factors. Asthma incidence was analyzed during a 2-year follow-up among centrally obese and nonobese groups in baseline children without asthma. MEASUREMENTS AND MAIN RESULTS: Central obesity most accurately predicts asthma. Low physical fitness levels and high screen time increase the risk of central obesity, which leads to asthma development. Obesity-related reduction in pulmonary function is a possible mechanism in the pathway from central obesity to asthma. CONCLUSIONS: Central obesity measures should be incorporated in childhood asthma risk predictions. Children are encouraged to increase their physical fitness levels and reduce their sedentary time to prevent central obesity-related asthma.

Association of urine CC16 and lung function and asthma in Chinese children.

BACKGROUND: Many studies have shown the relationship between serum Club cell secretory protein-16 (CC16) and respiratory diseases. However, little research has been done to study urinary CC16 in relation to respiratory diseases. Our objective was to examine the association of urinary CC16 and physician-diagnosed asthma or lung function measurements in Chinese children. METHODS: A total of 147 physician-diagnosed children with asthma, ages 9-15 years, were recruited from our cross-sectional study population in northeast China. The 390 healthy children who were not asthmatic and not smokers were selected at random from the population according to 10% proportional sampling. Lung function values, including forced expiratory volume in 1 second and forced vital capacity were measured with two portable spirometers. Urine CC16 was determined by using an enzyme-link immunoassay kit. The relationships between urine CC16 levels and asthma, lung function were assessed by multiple regression models. RESULTS: The geometric mean (95% confidence interval [CI]) creatinine-adjusted urine CC16 level was, for creatinine, 9.77 ng/mg (95% CI, 8.12-12.02 ng/mg). After adjustments for sex, age, body mass index, parental education, and smoking status, lower urine CC16 levels were found to be associated with asthma (odds ratio 0.782 [95% CI, 0.617- 0.990]). A positive association was found between urine CC16 and forced vital capacity (beta 0.064 [95% CI, 0.008-0.119]). CONCLUSION: Our study demonstrated lower levels of urine CC16 and lung function in patients with asthma than in those patients without asthma. CC16 in urine may be a useful tool or biomarker for investigating lung epithelium integrity among children with asthma or lung injury.

Phthalate Metabolites in Urine Samples from School Children in Taipei, Taiwan.

In 2011, Taiwan authorities reported that two phthalates, including di-(2-ethylhexyl) phthalate and di-iso-nonyl phthalate, were intentionally introduced into a variety of foods and beverages during the course of 15 years. However, little is known about body burdens of phthalate contaminations in local residents, especially children recently living in Taiwan. In the present study, five target phthalate metabolite analytes-including mono-methyl phthalate, mono-ethyl phthalate, mono-n-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), and mono-(2-ethylhexyl) phthalate (MEHP)-in spot urine samples were analyzed by way of high performance liquid chromatography-tandem mass spectrometry-mass spectrometry. All of the urine samples were collected from 225 healthy school children between 12 and 15 years of age (average 13.6) in the Taipei area, Taiwan, between 2009 and 2010. As the dominant urinary phthalate metabolites in Taiwanese school children, MEHP and MBP contributed 61 and 29 % of all of the target analytes, respectively. MEHP had the highest median of 29.8 µg/g creatinine (range of 13.1-72.8), which was greater than those reported for school children in the other countries during the same period, whereas MBP had a median of 14.3 µg/g creatinine (range 7.91-27.8). Statistically, urinary concentrations of MBP, MBzP, and MEHP were determined to have significantly positive correlations with the ages of Taiwanese school children (p < 0.05). Furthermore, urinary levels of MBzP in male children were considerably greater than those in female children (p = 0.006).

Asthma incidence, remission, relapse and persistence: a population-based study in southern Taiwan.

BACKGROUND: In western countries, late-onset asthmatics are more severe than early-onset asthmatics in clinic-based studies. However, whether asthma occurrence rates were higher in late ages than in younger ages was inconclusive. This information is essentially lacking in Asian population. METHODS: The participants were schoolchildren's parents recruited from 94 elementary and middle schools in 2004. A cross-sectional self-administered questionnaire was sent through the children to their parents to survey their respiratory health. We investigated typical asthma symptoms occurring at different ages and subsequent remission or relapse after the first asthma event. Person-years of the participants from birth to the time of survey were used as the denominator. RESULTS: Among the 25,377 participants consisting of 949,807 total person-years, 860 reported ever having asthma. Highest incidences occurred at ages 0-12 and 36-40 years. The incidence of asthma was higher in males before puberty, and higher in females after puberty, with overall incidences 1.00 and 0.77 per 1000 person-years for females and males, respectively. Participants with late-onset asthma (onset age >12 years) comprised a large portion of adult current asthmatics. More than 52% of persistence or relapse was observed in early-onset asthma (onset age ≤12 years). The younger birth cohort had a more prominent later peak of asthma incidence than the older one. CONCLUSIONS: In Asian population, asthma occurrence showed a U-shape age distribution with a prominent second peak in the thirties. A high proportion of early-onset asthma relapsed and most of late-onset asthma persisted or relapsed in adulthood.