Impact of the synergistic effect of pneumonia and air pollutants on newly diagnosed pulmonary tuberculosis in southern Taiwan.

BACKGROUND: An increased incidence of pulmonary tuberculosis (PTB) among patients with pulmonary diseases exposed to air pollution has been reported. OBJECTIVE: To comprehensively investigate the association between pneumonia (PN) and air pollution with PTB through a large-scale follow-up study. METHODS: We conducted a retrospective study using data from the Kaohsiung Medical University Hospital Research Database and the Taiwan Air Quality Monitoring Database. We included adult patients with PN, PTB and other comorbidities according to ICD-9 codes. Control subjects without PN were matched by age, sex and ten comorbidities to each PN patient at a ratio of 4:1. RESULTS: A total of 82,590 subjects were included. The PTB incidence rate was significantly higher in the PN group (2,391/100,000) than in the control group (1,388/100,000). The crude hazard ratio (HR) of PN-associated PTB incidence decreased with time, and the overall 7 years the HR (95% confidence interval; CI) was 1.74 (1.55-1.96). The overall adjusted HR and 95% CI of PN-related PTB in the multivariate Cox regression analysis was 3.38 (2.98-3.84). In addition, there was a cumulative lag effect of all air pollutants within 30 days of exposure. The peak adjusted HRs for PTB were noted on the 3rd, 8th, 12th and 12th days of PM2.5, O3, SO2 and NO exposure, respectively. The overall peak HRs (95% CI) of PM2.5, O3, SO2 and NO were 1.145 (1.139-1.152), 1.153 (1.145-1.161), 1.909 (1.839-1.982) and 1.312 (1.259-1.367), respectively, and there was a synergistic effect with pneumonia on the risk of PTB. CONCLUSIONS: A strong association was found between past episodes of PN and the future risk of PTB. In addition, air pollutants including PM2.5, SO2, O3 and NO, together with previous episodes of PN, had both long-term and short-term impact on the incidence of PTB.

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.

Pin1 coordinates HDAC6 upregulation with cell migration in lung cancer cells.

Histone deacetylase 6 (HDAC6) controls many cellular processes via its catalyzing deacetylation of downstream substrates or interacting with its partner proteins. Dysregulation of HDAC6 signaling links to many diseases. Our previous study has been reported peptidyl-prolyl cis/trans isomerase, and NIMA-interacting 1 (Pin1) involving in HDAC6-mediated cell motility. To gain insight into precisely coordination of HDAC6 and Pin1 in cell migration, shRNA-mediated gene silencing and ectopic expression were applied to manipulate protein expression level to evaluate relationship between HDAC6 and Pin1 expression. Quantitative RT-PCR and the cycloheximide (CHX) chase assay resulted in HDAC6 expression is correlated with Pin1 level in H1299 cells. It hints that the Pin1 increases HDAC6 expression through increased transcripts and posttranslational stabilization. Furthermore, wound healing assay and transwell invasion assay evidenced the contribution of Pin1 on cell motility in H1299 cells. Our data suggest that Pin1 acts as an important regulator to manage HDAC6 expression for cell motility in lung cancer cells.

Changes in clinical trials of cancer drugs in mainland China over the decade 2009-18: a systematic review.

As a result of recent, substantial capacity building, a new landscape for cancer drug trials is emerging in China. However, data on the characteristics of cancer drug trials, and how they have changed over time, are scarce. Based on clinical trials published on the China Food and Drug Administration Registration and Information Disclosure Platform for Drug Clinical Studies, we aimed to systematically review changes over time in clinical trials of cancer drugs in mainland China from 2009 to 2018, to provide insight on the effectiveness of the pharmaceutical industry and identify unmet clinical needs of stakeholders. A total of 1493 trials of 751 newly tested cancer drugs were initiated. Increases over time were observed for the annual number of initiated trials, newly tested drugs, and newly added leading clinical trial units, with a sharp increase after 2016. Of the 1385 trials in which cancer types were identified, solid tumours (325 [23%] trials), non-small-cell lung cancer (232 [17%]), and lymphoma (126 [9%]) were the most common. A markedly uneven distribution was also observed in the geography of leading units with the largest number of leading units located in east China (50 [41%]) and the smallest number located in southwest China (4 [3%]). The growth trends we observed illustrate the progress in and increasing capability of cancer drug research and development achieved in mainland China over the decade from 2009. The low number of clinical trials on tumours with epidemiological characteristics unique to the Chinese population and the unbalanced geographical distribution of leading clinical trial units will provide potential targets for policy makers and other stakeholders. Further research efforts should address cancers uniquely relevant to Chinese populations, globally rare cancers, and the balance between equitable drug access, efficiency, and sustainability of cancer drug research and development in mainland China.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

[Analysis on quality and differences of Mentha haplocalyx from different regions].

A gas chromatography-mass spectrometry(GC-MS)method was established for the analysis of volatile components in Mentha haplocalyx, and seven principal components were quantified by gas chromatography(GC). Based on these analyses, the differences of volatile components in M. haplocalyx from Jiangsu, Anhui and other regions were compared. The results showed that the volatile oil of M. haplocalyx was divided into four chemical types：menthol-menthone type, pulegone-menthone type, piperitone-menthol type, piperitone epoxide type, and menthol-menthone type was the principal type. Menthol was the highest and pulegone was the lowest. The differences of M. haplocalyx from Anhui and other regions were obvious. The major volatile components and the differences of M. haplocalyx from different regions were confirmed and a quantitative method was established for the determination of volatile components, which provided the basis for improving the quality standard of M. haplocalyx.

[Qualitative and Quantitative Analysis of Major Constituents of Gland Products in Peltate Glandular Trichomes of Schizonepetae Spica].

Objective: A method was established for separation, purification, enrichment and enumeration of peltate glandular trichomes from Schizonepetae Spica which combined with qualitative and quantitative analysis of major constituents of its inclusions. Methods: Frozen brush method and sedimentation of water concentration connected to technology of materials affinity were applied to separate and concentrate peltate glandular trichomes respectively, and extracts of inclusions was qualified by GCMS. Microscope enumeration was considered used to quantitatively analyze three monoterperes in single peltate glandular trichome and the calyx of Schizonepetae Spica. Results: 29 chemical compounds were identified from peltate glandular trichomes' inclusions of Schizonepetae Spica,constituting 97. 45% of the total peak area. 35 characteristic common peaks exceeding 97% of the total peak area was both present in peltate glandular trichomes' inclusions and essential oils of Schizonepetae Spica. The difference contents of d-limonene, dl-menthone, pulegone, E-carveol acetate, et al between peltate glandular trichomes' inclusions and essential oils of Schizonepetae Spica were large. The content of d-limonene,dl-menthone, pulgone in a single peltate glandular trichome was 27. 660,24. 334 and 396. 390 ng respectively through the method of microscope enumeration. Conclusion: The research provides a method of separation, purification enrichment and enumeration of peltate glandular trichomes. The chemical constituent of essential oil which is extracted by water vapor is different from peltate glandular trichomes' inclusions and could not reflect the ratio and content, while prediction model which based on microscope enumeration is precision.

Comparison of quantitative computed tomography analysis and single-indicator thermodilution to measure pulmonary edema in patients with acute respiratory distress syndrome.

OBJECTIVE: To compare quantitative computed tomography (CT) analysis and single-indicator thermodilution to measure pulmonary edema in patients with acute respiratory distress syndrome (ARDS). METHOD: Ten patients with ARDS were included. All underwent spiral CT of the thorax for estimating gas content of lung (GVCT), tissue volume of lung (TVCT), tissue volume index (TVI), mean radiographic attenuation (CTmean) for the whole lung and gas-to-tissue ratio (g/t). Pulmonary thermal volume (PTV) and extravascular lung water index (ELWI) were determined by the PiCCO plus system. CT or single-indicator thermodilution variables were correlated with respiratory system compliance (Crs), PaO2/FiO2, and Acute Physiology And Chronic Health EvaluationII (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. RESULTS: 1) TVCT and PTV were positively correlated (r =0.8878; P = 0.0006; equation of regression line: PTV = 1.0793 × TVCT + 179.8) as were TVI and ELWI (r =0.9459; P < 0.0001; equation of regression line: ELWI = 1.4506 × TVI-8.7792). The bias between TVCT and PTV as well as TVI and ELWI was -277 ± 217 and 0.62 ± 4.56, respectively. 2) ELWI and CT distribution of lung-tissue compartments were not correlated. 3) CT or single-indicator thermodilution variables were not correlated with Crs, PaO2/FiO2 or APACHE II or SOFA score. CONCLUSION: Quantitative CT analysis and single-indicator thermodilution showed good agreement in measuring pulmonary edema.

[Multi-level identification and analysis about infrared spectroscopy of lophatheri herba].

Based on the infrared spectra of Lophatheri Herba and Commelinae Herba, one-dimensional infrared spectra, second derivative spectra and two-dimensional correlated spectra were used to find out the differences between Lophatheri Herba and its imitations, respectively. The common peak ratio and variant peak ratio dual-indexes sequential were calculated and established according to infrared spectra of eleven batches of herbs. Infrared spectral data of Lophatheri Herba cluster analysis was applied to explore the similarity between each sample. The grouping results trend of sequential analysis of dual-indexes and cluster analysis was accordant. The results showed that the differences could be found by multi-level identification, and the source and the quality of the herbs could be effectively distinguished by the two analysis methods. Infrared spectroscopy, used in the present work exhibited some advantages on quick procedures, less sample required, and reliable results, which could provide a new method for the identification of traditional Chinese medicine with the imitations and adulterants, and the control of quality and origin.

The association of peritoneal dialysis and hemodialysis on mitral and aortic valve calcification associated mortality: a meta-analysis.

Cardiac valve calcification (CVC), characterized by the accumulation of calcium in the heart valves, is highly prevalent among patients undergoing dialysis. This meta-analysis aimed to provide an updated summary of recent studies on the prognostic value of CVC in patients undergoing dialysis. We conducted a search of PubMed, Embase, and Web of Science to identify observational studies investigating cardiovascular or all-cause mortality associated with CVC in dialysis patients until March 2023. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated for the meta-analysis, and the strength and significance of the associations between CVC and mortality outcomes in dialysis patients were assessed. From 6218 initially identified studies, we included 10 critical studies with a total of 3376 dialysis patients in a further meta-analysis. Pooled analyses demonstrated a significant association between CVC and an elevated risk of all-cause and cardiovascular mortality in dialysis patients. In our study, we discovered HRs of 1.592 (95% CI 1.410-1.797) for all-cause mortality and 2.444 (95% CI 1.632-3.659) for cardiovascular mortality. Furthermore, subgroup analysis revealed elevated all-cause mortality among patients with mitral valve calcification (HR 1.572; 95% CI 1.200-2.060) compared to those with aortic valve calcification (HR 1.456; 95% CI 1.105-1.917). Similarly, patients undergoing peritoneal dialysis faced a greater risk for all-cause mortality (HR 2.094; 95% CI 1.374-3.191) than those on hemodialysis (HR 1.553; 95% CI 1.369-1.763). This highlights the possibility of CVC being an independent risk factor for dialysis patients, particularly in relation to mitral valve calcification or peritoneal dialysis.

Association between air pollutants with calcaneus ultrasound T-score change in a large Taiwanese population follow-up study.

Exposure to ambient air pollution has been associated with increased rates of mortality and morbidity and a shorter life expectancy. Few studies have evaluated the associations between air pollution and change in calcaneus ultrasound T-score (∆T-score). Therefore, in this longitudinal study, we explored these associations in a large group of Taiwanese participants. We used data from the Taiwan Biobank database and Taiwan Air Quality Monitoring Database, which contains detailed daily data on air pollution. We identified 27,033 participants in the Taiwan Biobank database who had both baseline and follow-up data. The median follow-up period was 4 years. The studied ambient air pollutants included particulates of 2.5 µm or less (PM2.5), particulates of 10 µm or less (PM10), ozone (O3), carbon monoxide (CO), sulfur dioxide (SO2), nitric oxide (NO), nitrogen dioxide (NO2), and nitrogen oxide (NOx). Multivariable analysis showed that PM2.5 (ß, -0.003; 95% confidence interval (CI), -0.004 to -0.001; p < 0.001), PM10 (ß, -0.005; 95% CI, -0.006 to -0.004, p < 0.001), O3 (ß, -0.008; 95% CI, -0.011 to -0.004; p < 0.001), and SO2 (ß, -0.036; 95% CI, -0.052 to -0.020; p < 0.001) were negatively associated with ∆T-score, and that CO (ß, 0.344; 95% CI, 0.254, 0.433; p < 0.001), NO (ß, 0.011; 95% CI, 0.008 to 0.015; p < 0.001), NO2 (ß, 0.011; 95% CI, 0.008 to 0.014; p < 0.001), and NOx (ß, 0.007; 95% CI, 0.005 to 0.009; p < 0.001) were positively significantly associated with ∆T-score. Furthermore, PM2.5 and SO2 (ß, -0.014; 95% CI, -0.016 to -0.013; p < 0.001) and PM10 and SO2 (ß, -0.008; 95% CI, -0.009 to -0.007; p < 0.001) had synergistic negative effects on ∆T-score. In conclusion, we found that high PM2.5, PM10, O3, and SO2 were associated with a rapid decline in T-score, whereas high CO, NO, NO2, and NOx were associated with a slow decline in T-score. Furthermore, PM2.5 and SO2 and PM10 and SO2 had synergistic negative effects on ∆T-score, causing an acceleration in T-score decline. These findings may be helpful when developing policies on air pollution regulation.

Low Lung Function Is Associated with Low Baseline Calcaneus Ultrasound T-Score but a Slow Decline in T-Score in a Taiwanese Follow-Up Population with No History of Smoking, Bronchitis, Emphysema, or Asthma.

Osteoporosis is a common disease, and the prevalence is increasing in patients with chronic respiratory diseases, with important implications with regard to fractures, hospitalization, and death. Due to inconsistent data and a lack of large cohort follow-up studies on the association between lung function and osteoporosis, the aim of this study was to investigate this issue. We enrolled and followed for a median of 4 years a total of 9059 participants with no history of smoking, bronchitis, emphysema, or asthma from the Taiwan Biobank. Spirometry data, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were used to assess lung function. Changes in the calcaneus ultrasound T-score (ΔT-score) were calculated as follow-up T-score-baseline T-score. A ΔT-score ≤ -3 (median value of ΔT-score) meant a fast decline in T-score. Multivariable analysis showed that lower values of FEV1 (ß, 0.127, p < 0.001), FVC (ß, 0.203, p < 0.001), and FEV1/FVC (ß, 0.002, p = 0.013) were significantly associated with a low baseline T-score. In addition, after follow-up, higher values of FEV1 (odds ratio (OR), 1.146, p = 0.001), FVC (OR, 1.110, p = 0.042), and FEV1/FVC (OR, 1.004, p = 0.002) were significantly associated with ΔT-score ≤ -3. FEV1/FVC < 70% (OR, 0.838, p < 0.001) was significantly associated with ΔT-score ≤ -3. In conclusion, lower FEV1, FVC, and FEV1/FVC were associated with a low baseline T-score, and higher FEV1, FVC, and FEV1/FVC were associated with a rapid decline in T-score in follow-up. This suggests that lung disease may be associated with bone mineral density in the Taiwanese population with no history of smoking, bronchitis, emphysema, or asthma. Further research is needed to establish causality.

Association between ambient air pollutant interaction with kidney function in a large Taiwanese population study.

The associations and interactions between kidney function and other air pollutants remain poorly defined. Therefore, the aim of this study was to evaluate associations among air pollutants, including particulate matter (PM) with a diameter ≤ 2.5 µm (PM2.5), PM10 (PM with a diameter ≤ 10 µm), carbon monoxide (CO), nitrogen oxide (NO), nitrogen oxides (NOx), sulfur dioxide (SO2), and ozone (O3) with kidney function, and explore interactions among these air pollutants on kidney function. We used the Taiwan Air Quality Monitoring and Taiwan Biobank databases to derive data on community-dwelling individuals in Taiwan and daily air pollution levels, respectively. We enrolled 26,032 participants. Multivariable analysis showed that high levels of PM2.5, PM10, O3 (all p < 0.001), and SO2 (p = 0.001) and low levels of CO, NO (both p < 0.001), and NOx (p = 0.047) were significantly correlated with low estimated glomerular filtration rate (eGFR). With regard to negative effects, the interactions between PM2.5 and PM10 (p < 0.001), PM2.5 and PM10 (p < 0.001), PM2.5 and SO2, PM10 and O3 (both p = 0.025), PM10 and SO2 (p = 0.001), and O3 and SO2 (p < 0.001) on eGFR were significantly negatively. High PM10, PM2.5, O3, and SO2 were associated with a low eGFR, whereas high CO, NO, and NOx were associated with a high eGFR. Furthermore, negative interactions between PM2.5 and PM10, O3 and SO2, PM10 and O3, PM2.5 and SO2, and PM10 and SO2 on eGFR were observed. The findings of this study have important implications for public health and environmental policy. Specifically, the results of this study may be useful in individuals and organizations to take action to reduce air pollution and promote public health.

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.

The association between alcohol, betel nut, and cigarette use with hepatitis C virus infection in Taiwan.

Hepatitis C virus (HCV) infection may cause chronic liver disease, liver cirrhosis, and liver cancer. It has been reported to associate with habits including alcohol, betel nut and cigarette use. We aimed to investigate the association between alcohol, betel nut, and cigarette use with HCV infection in Taiwan and to explore their effects. A total of 121,421 participants were enrolled from the Taiwan Biobank. They were stratified into two groups according to whether they had (n = 2750; 2.3%) or did not have (n = 118,671; 97.7%) HCV infection. All participants were also classified into four groups according to the number of habits, including a history of alcohol drinking, betel nut chewing, and cigarette smoking. There were 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits) participants in the four groups, respectively. Multivariable analysis showed that the participants who had an alcohol drinking history (odds ratio [OR] 1.568; 95% confidence interval [CI] 1.388-1.773; p < 0.001), betel nut chewing history (OR 1.664; 95% CI 1.445-1.917; p < 0.001), cigarette smoking history (OR 1.387; 95% CI 1.254-1.535; p < 0.001), were significantly associated with HCV infection. Furthermore, the participants were classified into four groups according to the number of habits as follows: 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits). The HCV infection rates in these four groups were 2.11%, 2.14%, 3.23%, and 4.78%, respectively. Compared to the participants with no or one habit, those with two habits had a higher HCV infection rate (all p < 0.001). In addition, compared to the participants who had no, one or two habits, those who had three habits also had higher HCV infection rates (all p < 0.001). The participants who had three habits had the highest prevalence of HCV infection. In an era when most HCV can be cured, understanding the epidemiology link between habits and HCV may help the case finding.

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.