Associations of dermal diethyl phthalate level with changes in lung function test value mediated by absolute eosinophil count: A panel study of adults in southern Taiwan.

Phthalate concentrations in indoor and outdoor dust are associated with respiratory disease. Both immunoglobulin E (IgE) and eosinophil count are associated with airway inflammation from exposure to environmental allergens. Dermal phthalate level can be used as a matrix for assessing personal exposure through direct absorption from the air, particle deposition, or contact with contaminated products. However, the association between dermal phthalate level and changes in lung function test values, as mediated by immunological response, remains unclear. In total, 237 adults in southern Taiwan were recruited. Spirometry measurements (in L) of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were taken on visits 1 (2016-2018) and 2 (2019). Dermal phthalate level, absolute eosinophil count, and IgE level were recorded on visit 1. Mean changes in FVC and FEV1 decrease pear year, as determined through pairwise comparisons, were significant (diffFVCper year: -0.46, 95% CI: -0.51, -0.41; p < 0.001; diffFEV1per year: -0.37, 95% confidence interval [CI]: -0.41, -0.34; p < 0.001). For FEV1 decrease, log-unit increases in dermal diethyl phthalate (DEP) were positively associated with diffFEV1per year (ß = 0.096; 95% CI: 0.042, 0.150; p = 0.001) and negatively associated with absolute eosinophil count (ß= -0.201; 95% CI: -0.380, -0.023; p= 0.027). Log-unit increases in absolute eosinophil count were negatively associated with diffFEV1per year (ß= -0.109; 95% CI: -0.150, -0.068; p < 0.001). Absolute eosinophil count mediated 19.70% of the association between dermal DEP level and diffFEV1per year. For FVC decrease, log-unit increases in dermal DEP were positively associated with diffFVCper year (ß = 0.095; 95% CI: 0.035, 0.155; p = 0.002) and negatively associated with absolute eosinophil count (ß = -0.243; 95% CI: -0.427, -0.060; p = 0.010). Log-unit increases in absolute eosinophil count were negatively associated with diffFVCper year (ß= -0.122; 95% CI: -0.168, -0.076; p < 0.001). Absolute eosinophil count mediated 29.98% of the association between dermal DEP level and diffFVCper year. The results suggest that dermal DEP level is positively associated with changes in lung function test values and is mediated by absolute eosinophil count.

Clinical risk factors of prediabetes in Taiwanese women without substance uses (tobacco, alcohol, or areca nut).

BACKGROUND/PURPOSE: Individuals with prediabetes (100-125 mg/dL) and diabetes mellitus (DM) increase the risk of all-cause and cardiovascular disease (CVD) mortality. Since personal substance use such as cigarette smoking, alcohol drinking, and areca nut chewing may confound the true effect of clinical biochemistries on the risk of prediabetes, this study aims to examine the relationship between clinical biochemical parameters and the risk of prediabetes among Taiwanese without the habits of consuming tobacco, alcohol drinking, or areca nut. METHODS: Women aged between 40 years and 64 years who came to one community teaching hospital between January 1, 2001 and December 31, 2008 for general health screening for the first time were studied. The general health screening is provided every 3 years gratis. The package of this health screening includes personal history, physical examination, and biochemical tests in serum and urine. RESULTS: In total, 8580 nonsmoking, nondrinking, and nonareca nut chewing women who did not have a history of DM were eligible for this study. Of these, 1861 (21.7%) out of 8580 women were prediabetic. Compared to women with normal fasting glucose (NFG), we found a dose-response relationship of the risk of prediabetes with age and body mass index (BMI) and total cholesterol, triglyceride, glutamic-pyruvic transaminase (GPT), and uric acid in serum. Women with hypertension or proteinuria (≥30 mg/dL) had also an increased risk to have prediabetes. CONCLUSION: Besides age, the factors of BMI, hypertension, dyslipidemia, GPT, hyperuricemia, and proteinuria are the main risk factors for prediabetes in Taiwanese women without substance uses. A follow-up study is necessary to clarify the causality of these important biochemical parameters and prediabetes.

Arsenic exposure associated with lung interstitial changes in non-smoking individuals living near a petrochemical complex: A repeated cross-sectional study.

Arsenic exposure is associated with airway inflammation and decreased lung function tests. Whether arsenic exposure associated with lung interstitial changes remains unknown. We conducted this population-based study in southern Taiwan during 2016 and 2018. Our study recruited individuals aged over 20 years, residing in the vicinity of a petrochemical complex and with no history of cigarette smoking. In both the 2016 and 2018 cross-sectional studies, we conducted chest low-dose computed tomography (LDCT) scans, as well as urinary arsenic and blood biochemistry analyses. Lung interstitial changes included lung fibrotic changes that were defined as the presence of curvilinear or linear densities, fine lines, or plate opacity in specific lobes; additionally, other interstitial changes were defined as the presence of ground-glass opacity (GGO) or bronchiectasis on the LDCT images. In both cross-sectional studies conducted in 2016 and 2018, participants with lung fibrotic changes exhibited a statistically significant increase in the mean urinary arsenic concentrations compared to those without fibrotic changes (geometric mean = 100.1 vs. 82.8 µg/g creatinine, p < 0.001 for cross-sectional study 2016, and geometric mean = 105.6 vs. 71.0 µg/g creatinine, p < 0.001 for cross-sectional study 2018). After controlling for age, gender, body mass index, platelet counts, hypertension, aspartate aminotransferase, cholesterol, HbA1c, and educational levels, we observed a significant positive association between a unit increase in log urinary arsenic concentrations and the risk of lung fibrotic changes in both cross-sectional study 2016 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.04-1.90, p = 0.028) and cross-sectional study 2018 (OR = 3.03, 95% CI = 1.38-6.63, p = 0.006). Our study did not find a significant association between arsenic exposure and bronchiectasis or GGO. It is imperative for the government to take significant measures to reduce arsenic exposure levels among individuals living near petrochemical complexes.

Blood lead (Pb) is associated with lung fibrotic changes in non-smokers living in the vicinity of petrochemical complex: a population-based study.

Lead (Pb) is a toxic metal that has been extensively used in various industrial processes, and it persists in the environment, posing a continuous risk of exposure to humans. This study investigated blood lead levels in participants aged 20 years and older, who resided in Dalinpu for more than two years between 2016 to 2018, at Kaohsiung Municipal Siaogang Hospital. Graphite furnace atomic absorption spectrometry was used to analyze the blood samples for lead levels, and the LDCT (Low-Dose computed tomography) scans were interpreted by experienced radiologists. The blood lead levels were divided into quartiles, with Q1 representing levels of ≤1.10 µg/dL, Q2 representing levels of >1.11 and ≤1.60 µg/dL, Q3 representing levels of >1.61 and ≤2.30 µg/dL, and Q4 representing levels of >2.31 µg/dL. Individuals with lung fibrotic changes had significantly higher (mean ± SD) blood lead levels (1.88±1.27vs. 1.72±1.53 µg/dl, p< 0.001) than those with non-lung fibrotic changes. In multivariate analysis, we found that the highest quartile (Q4: >2.31 µg/dL) lead levels (OR: 1.36, 95% CI: 1.01-1.82; p= 0.043) and the higher quartile (Q3: >1.61 and ≤2.30 µg/dL) (OR: 1.33, 95% CI: 1.01-1.75; p= 0.041) was significantly associated with lung fibrotic changes compared with the lowest quartile (Q1: ≤1.10 µg/dL) (Cox and Snell R2, 6.1 %; Nagelkerke R2, 8.5 %). The dose-response trend was significant (Ptrend= 0.030). Blood lead exposure was significantly associated lung fibrotic change. To prevent lung toxicity, it is recommended to maintain blood lead levels lower than the current reference value.

Arsenic exposure and lung fibrotic changes-evidence from a longitudinal cohort study and experimental models.

Introduction: Arsenic (As) exposure is associated with lung toxicity and we aim to investigate the effects of arsenic exposure on lung fibrotic changes. Methods: Participants (n= 976) enrolled via a general health survey underwent chest low-dose computed tomography (LDCT), spirometry forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and urinary arsenic examination during 2016 and 2018. Lung fibrotic changes from LDCT were defined. AsLtoL, low arsenic levels in both 2016 and 2018; AsLtoH, low arsenic in 2016 but high levels in 2018; AsHtoL, high arsenic in 2016 but low levels in 2018; AsHtoH, high arsenic levels in both 2016 and 2018. Mice exposed to 0. 0.2mg/L, 2 mg/L, 50 mg/L of sodium arsenite (NaAsO2) through drinking water for 12 weeks and 24 weeks were applied for histological analysis. Cultured lung epithelial cells were exposed to NaAsO2 and the mesenchymal changes were examined. Results: AsHtoH increased the risk (OR= 1.65, 95% CI 1.10, 2.49) of Lung fibrotic positive to positive (reference: Lung fibrotic negative to negative) compared with AsLtoL. Moreover, the predicted mean of FVC and FEV1 in AsHtoH (-0.09 units, 95% CI: -0.27, -0.09; -0.09 units, 95% CI: -0.17, -0.01) and AsLtoH (-0.13 units, 95% CI: -0.30, -0.10; -0.13 units, 95% CI: -0.22, -0.04) was significantly lower than ASLtoL. Significant lung fibrotic changes including the increase of the alveolar septum thickness and collagen fiber deposition were observed upon 2 mg/L NaAsO2 treatment for 12 weeks, and the damage was dose- and time-dependent. In vitro, sodium arsenite treatment promotes the epithelial-mesenchymal transition (EMT)-like changes of the normal human bronchial epithelial cells, including upregulation of several fibrotic and mesenchymal markers (fibronectin, MMP-2, and Snail) and cell migration. Inhibition of reactive oxygen species (ROS) and MMP-2 impaired the arsenic-induced EMT changes. Administration of a flavonoid, apigenin, inhibited EMT in vitro and pulmonary damages in vivo with the reduction of mesenchymal markers. Discussion: we demonstrated that continued exposure to arsenic causes lung fibrosis in humans and mice. Targeting lung epithelial cells EMT is effective on the development of therapeutic strategy. Apigenin is effective in the inhibition of arsenic-induced pulmonary fibrosis and EMT.

Effect of dermal phthalate levels on lung function tests in residential area near a petrochemical complex.

Phthalates can leach into indoor and outdoor airborne particulate matter and dust, which can then be ingested or absorbed and induce lung injury. Dermal phthalate levels can be used as a matrix for exposure direct absorption from air, particle deposition, and contact with contaminated products. However, the association between dermal phthalate levels in skin wipes and lung function tests remains unknown. A total of 397 participants were included. Spirometry measurements of forced expiratory volume in 1 s (FEV1, L) and forced vital capacity (FVC, L) were calculated. Dermal phthalate levels of diethyl phthalate (DMP), diethyl phthalate (DEP), di(n-butyl) phthalate (DnBP), butyl benzyl phthalate (BBzP), di(2-ethylhexyl) phthalate (DEHP), diisononyl phthalate (DiNP), and diisodecyl phthalate (DiDP) on forehead skin wipes were detected. The one-unit increases in logarithm (log) dermal DnBP (ß = - 0.08; 95% CI - 0.16, - 0.003, p = 0.041), BBzP (ß = - 0.09; 95% CI - 0.16, - 0.02, p = 0.009), DEHP (ß = - 0.07; 95% CI - 0.14, - 0.003, p = 0.042), and DiNP (ß = - 0.08; 95% CI - 0.15, - 0.02, p = 0.017) were significantly associated with decreases in FVC. For elderly participants, one-unit increases in log dermal DnBP (ß = - 0.25; 95% CI - 0.46, - 0.04, p = 0.021), BBzP (ß = - 0.17; 95% CI - 0.33, - 0.01, p = 0.042), and DiDP (ß = - 0.19; 95% CI - 0.39, < 0.01, p = 0.052) were associated with decreases in FEV1. In conclusion, dermal phthalate levels were significantly associated with decreases in lung function tests.

Association study of LIN28B in girls with precocious puberty.

BACKGROUND: Central precocious puberty (CPP), predominant in girls, is defined by early development of secondary sexual characteristics driven by the early secretion of hypothalamic gonadotropin releasing hormone (GnRH) and subsequent gonadotropin. Recent studies have shown variation in the LIN28B gene is associated with timing of puberty, but only a few have show it to be associated with CPP. METHODS: This study attempted to investigate the relation between single-nucleotide polymorphisms (SNPs) in LIN28B and girls with precocious puberty. Genotype and alleles frequencies of selected SNPs were compared between 116 girls with CPP and 102 controls. RESULTS: We found genotype frequencies in rs314276 and rs221634 were significantly correlated with girls with CPP; while the C allele frequency in rs314276 showed the dominant trait. Standard deviation score (SDS) of weight and body mass index (BMI) were higher in CC homozygotes of rs314276 in girls with CPP. CONCLUSIONS: Our results demonstrate that the genotype of rs314276 in LIN28B is associated with girls with CPP, carrying dominant trait in the C allele.

Association between GABA(A) receptor subunit gene cluster and zolpidem-induced complex sleep behaviors in Han Chinese.

STUDY OBJECTIVES: To investigate and elucidate the role of GABA(A) receptor subunits, specifically the 2 genetic markers at the GABA(A) α1 and GABA(A) α6 receptors, in zolpidem-induced complex sleep behaviors (CSBs). DESIGN: Genetic association study. SETTING: Kaohsiung Medical University-affiliated hospitals, Kaohsiung, Taiwan. PATIENTS: 30 zolpidem-induced CSB subjects and 37 controls. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The χ(2) test demonstrated an association between the A15G variant at the GABA(A) α1 receptor subunit gene and zolpidem-induced CSBs (P = 0.007). The adjusted odds ratio of the GABA(A) α1 receptor subunit genotype for the risk of zolpidem-induced CSBs was approximately 10 (OR = 9.99, 95% CI = 1.82, 74.87; P = 0.013). CONCLUSIONS: The finding reveals that the A15G variant at the GABA(A) α1 receptor subunit gene confers a high risk of zolpidem-induced CSBs and may be considered in clinical services.