Effects of Heart Rate Variability (HRV) Biofeedback in Pulmonary Indicators and HRV Indices Among Patients with Chronic Obstructive Pulmonary Disease.

Patients with chronic obstructive pulmonary disease (COPD) exhibit reduced cardiac autonomic activity, linked to poor prognosis and exercise intolerance. While heart rate variability biofeedback (HRVB) can enhance cardiac autonomic activity in various diseases, its use in patients with COPD is limited. This study explored the impact of the HRVB on cardiac autonomic activity and pulmonary indicators in patients with COPD. Fifty-three patients with COPD were assigned to either the HRVB (n = 26) or the control group (n = 27), with both groups receiving standard medical care. The HRVB group also underwent one-hour HRVB sessions weekly for six weeks. All participants had pre- and post-test measurements, including the Six-Minute Walking Test (6MWT), lead II electrocardiogram (ECG) recording, Modified Medical Research Council Dyspnea Scale (mMRC), body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index. ECG data were analyzed for heart rate variability (HRV) as an index of cardiac autonomic activity. A two-way mixed analysis of variances demonstrated significant interaction effects of Group × Time in pulmonary indicators and HRV indices. The HRVB group exhibited significant post-test improvements, with decreased mMRC and BODE scores and increased 6MWT distance and HRV indices, compared to pre-test results. The 6MWT distance significantly increased and mMRC significantly decreased at post-test in the HRVB group compared with the control group. This study confirmed the efficacy of HRVB as an adjunct therapy in patients with COPD, showing improvements in exercise capacity, breathing difficulties, and cardiac autonomic activity.

Personalized neoantigen cancer vaccines: current progression, challenges and a bright future.

Tumor neoantigens possess specific immunogenicity and personalized therapeutic vaccines based on neoantigens which have shown promising results in some clinical trials, with broad application prospects. However, the field is developing rapidly and there are currently few relevant review articles. Summarizing and analyzing the status of global personalized neoantigen vaccine clinical trials will provide important data for all stakeholders in drug development. Based on the Trialtrove database, a retrospective analysis was conducted using trial quantity as a key indicator for neo-adjuvant and adjuvant therapy anti-PD-1/PD-L1 clinical trials initiated before the end of 2022. The time trend of newly initiated trials was investigated. The sponsor type, host country, treatment mode, combination strategy, tested drugs, and targeted cancer types of these trials were summarized. As of December 2022, a total of 199 trials were included in the analysis. Among these studies, Phase I studies were the most numerous (119, 59.8%), and Phase I studies have been the predominant study type since 2015. Peptide vaccines were the largest neoantigen vaccines type, accounting for 64.8% of all clinical trials. Based on peptide delivery platforms, the proportion of trials was highest for the DC system (32, 16.1%), followed by LNP (11, 5.5%), LPX (11, 5.5%), and viruses (7, 3.5%). Most vaccines were applied in trials as a monotherapy (133/199, 66.8%), meanwhile combining immunotherapeutic drugs was the most common form for combination therapy. In terms of indications, the largest number of trials involved three or more unspecified solid tumors (50/199, 25.1%), followed by non-small cell lung cancer (24/199, 12.1%) and pancreatic cancer (15/199, 7.5%). The clinical development of personalized neoantigen cancer vaccines is still in the early stage. A clear shift in delivery systems from peptides to DC and liposomal platforms, with the largest number of studies in Asia, collectively marks a new era in the field. The adjuvant or maintenance therapy, and the combination treatment with ICIs are becoming the important clinical development orientation. As research on tumor-immune interactions intensifies, the design, development, and application of neoantigen vaccines are bound to develop rapidly, which will bring a new revolution in the future cancer treatment.

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.

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.

The impact of the synergistic effect of SO2 and PM2.5/PM10 on obstructive lung disease in subtropical Taiwan.

Background: Chronic Obstructive lung diseases (COPD) are complex conditions influenced by various environmental, lifestyle, and genetic factors. Ambient air pollution has been identified as a potential risk factor, causing 4.2 million deaths worldwide in 2016, accounting for 25% of all COPD-related deaths and 26% of all respiratory infection-related deaths. This study aims to evaluate the associations among chronic lung diseases, air pollution, and meteorological factors. Methods: This cross-sectional study obtained data from the Taiwan Biobank and Taiwan Air Quality Monitoring Database. We defined obstructive lung disease as patients with FEV1/FVC < 70%. Descriptive analysis between spirometry groups was performed using one-way ANOVA and the chi-square or Fisher's exact test. A generalized additive model (GAM) was used to evaluate the relationship between SO2 and PM2.5/PM10 through equations and splines fitting. Results: A total of 2,635 participants were enrolled. Regarding environmental factors, higher temperature, higher relative humidity, and lower rainfall were risk factors for obstructive lung disease. SO2 was positively correlated with PM10 and PM2.5, with correlation coefficients of 0.53 (p < 0.0001) and 0.52 (p < 0.0001), respectively. Additionally, SO2 modified the relative risk of obstructive impairment for both PM10 [ß coefficient (ß) = 0.01, p = 0.0052] and PM2.5 (ß = 0.01, p = 0.0155). Further analysis per standard deviation (per SD) increase revealed that SO2 also modified the relationship for both PM10 (ß = 0.11, p = 0.0052) and PM2.5 (ß = 0.09, p = 0.0155). Our GAM analysis showed a quadratic pattern for SO2 (per SD) and PM10 (per SD) in model 1, and a quadratic pattern for SO2 (per SD) in model 2. Moreover, our findings confirmed synergistic effects among temperature, SO2 and PM2.5/PM10, as demonstrated by the significant associations of bivariate (SO2 vs. PM10, SO2 vs. PM2.5) thin-plate smoothing splines in models 1 and 2 with obstructive impairment (p < 0.0001). Conclusion: Our study showed high temperature, humidity, and low rainfall increased the risk of obstructive lung disease. Synergistic effects were observed among temperature, SO2, and PM2.5/PM10. The impact of air pollutants on obstructive lung disease should consider these interactions.

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.

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.

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.

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.