Association of long-term exposure to PM2.5 and survival following ischemic heart disease.

BACKGROUND: Numerous studies have suggested that long-term exposure to particulate matter ≤2.5 µm (PM2.5) may cause cardiovascular morbidity and mortality. However, susceptibility among those with a history of ischemic heart disease is less clearly understood. We aimed to evaluate whether long-term PM2.5 exposure is related to mortality among patients with ischemic heart disease. METHODS: We followed up 306,418 patients hospitalized with ischemic heart disease in seven major cities in South Korea between 2008 and 2016 using the National Health Insurance Database. We linked the modeled PM2.5 data corresponding to each patient's administrative districts and estimated hazard ratios (HRs) of cause-specific mortality associated with the long-term exposure to PM2.5 in time-varying Cox proportional hazard models after adjusting for individual- and area-level characteristics. We also estimated HRs by sex, age group (65-74 vs. ≥75 years), and household income. RESULTS: Of the patients with ischemic heart disease, mean age at the discharge was 76.8 years, and 105,913 died during a mean follow-up duration of 21.4 months. The HR of all-cause mortality was 1.10 [95% confidence intervals (CI): 1.07, 1.14] per 10 µg/m3 increase in a 12-month moving average PM2.5. The HRs of cardiovascular, stroke, and ischemic heart disease were 1.17 (95% CI: 1.11, 1.24), 1.17 (95% CI: 1.06, 1.30), and 1.25 (95% CI: 1.15, 1.35), respectively. The subgroup analyses showed that participants aged 65-74 years were more susceptible to adverse effects of PM2.5 exposure. We did not observe any differences in the risk by sex and household income. CONCLUSION: Mortality from all-cause and cardiovascular disease following hospitalization due to ischemic heart disease was higher among individuals with greater PM2.5 exposure in seven major cities in South Korea. The result supports the association of long-term exposure to air pollution with poor prognosis among patients with ischemic heart disease.

Impact of Induction Immunosuppressants on T Lymphocyte Subsets after Kidney Transplantation: A Prospective Observational Study with Focus on Anti-Thymocyte Globulin and Basiliximab Induction Therapies.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4+ T cell expression decreased significantly compared with that in the BXM group. However, CD4+CD161+ and CD4+CD25+CD127low T cell expression levels increased significantly. In the CD8+ T cell subset, a decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4+CD161+ and CD4+CD25+CD127low T cells and an early decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cells, some of which are associated with acute rejection.

Particulate air pollution and survival after stroke in older adults: A retrospective cohort study in Korea.

Although many studies have evaluated the effects of ambient particulate matter with diameters of less than 2.5 µm (PM2.5) on stroke mortality in the general population, little is known about the mortality effects of PM2.5 in post-stroke populations. Therefore, a retrospective cohort was constructed using information from the health insurance database to evaluate whether exposure to PM2.5 is associated with increased mortality in aged stroke survivors residing in seven Korean metropolitan cities. A total of 45,513 older adults (≥65 years) who visited emergency rooms due to stroke and who were discharged alive between 2008 and 2016 were followed up. By using district-level modeled PM2.5 concentrations and a time-varying Cox proportional hazard model, associations between 1-month and 2-month moving average PM2.5 exposures and mortality in stroke survivors were evaluated. The annual average concentration of PM2.5 was 27.9 µg/m3 in the seven metropolitan cities, and 14,880 subjects died during the follow-up period. A 10 µg/m3 increase in the 1-month and 2-month moving average PM2.5 exposures was associated with mortality hazard ratios of 1.07 (95% confidence interval: 1.05, 1.09) and 1.06 (95% confidence interval: 1.03, 1.08), respectively. The effects of PM2.5 were similar across types of stroke (ischemic and hemorrhagic), age groups (65-74, 75-84, and ≥85), and income groups (low and high) but were greater in women than in men. This study highlights the adverse health effects of ambient PM2.5 in post-stroke populations. Active avoidance behaviors against PM2.5 are recommended for aged stroke survivors.

Short-term exposure to air pollution and hospital admission for heart failure among older adults in metropolitan cities: a time-series study.

PURPOSE: We aimed to investigate the association between air pollution concentration levels and hospital admissions for heart failure (HF) among older adults in metropolitan cities in South Korea. METHODS: We used hospital admission data of 1.8 million older adults in seven metropolitan cities from 2008 to 2016, derived from the National Health Insurance Service of South Korea. Daily HF admission data were linked to air pollutants concentrations for the respective dates, including particulate matter less than 2.5 µm in size (PM2.5), 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone. We estimated the association between air pollutants and daily HF admissions using quasi-Poisson generalized additive models for each city. RESULTS: During the study period, 142,490 hospital admissions for HF were noted. Increases of 10 µg/m3 of PM2.5 and PM10, and 10 ppb of SO2, NO2, and CO were associated with an increased risk of HF admission by 0.93% ([95% confidence intervals 0.51-1.36], 0.55% [0.31-0.80], 6.04% [2.15-10.08], 1.10% [0.38-1.82], and 0.05% [0.01-0.09]), respectively, on the same day. Increases in mean exposure to PM2.5, PM10, and SO2 for 8 days from the concurrent day were also significantly associated with HF admissions. During the warm season, the risk of HF admissions increased shortly after an increase in PM2.5, whereas prolonged effects were observed during the cold season. CONCLUSION: Our study suggests the adverse effects of air pollution on HF. Moreover, the evidence of seasonality may help tailor protection guidelines for older adults.

Source country-specific burden on health due to high concentrations of PM2.5.

Asian countries face frequent spikes in concentrations of particulate matter smaller than 2.5 µm (PM2.5), which may consist of domestic emissions, transported pollutants from neighboring countries, and secondary aerosol formation (SAF). We aimed to estimate the burden on health in South Korea due to PM2.5 exposure from source countries. We computed the health benefits of meeting air quality guidelines during high pollution periods or spike periods. We used daily mortality counts, PM2.5 concentrations, and primary and secondary contributions to pollutant levels in seven cities and nine provinces in South Korea during 2006-2016. Generalized additive mixed modeling with a Poisson distribution and random effects in 16 regions was used to examine the short-term effects of PM2.5 on mortality. We computed attributable burden due to PM2.5 exposure and the potential benefits of meeting the air quality guidelines set by the World Health Organization (WHO, 25 µg/m3) and the Korea Ministry of Environment (50 and 35 µg/m3 before and after 2015, respectively). A concentration-response curve showed a non-linear relationship between daily mortality counts and PM2.5 levels. The short-term health impacts of PM2.5 were suggested to be 1638 non-accidental deaths in 2016 in South Korea due to daily domestic emissions and pollutants transported from neighboring countries. Of these, 1509, 995, or 238 deaths could have been prevented if the daily mean PM2.5 concentration had been kept below 25, 35, or 50 µg/m3. After accounting for the contribution of SAF to PM2.5, primary sources of PM2.5 resulted in 258-860 and 26-88 deaths due to pollution transported from China and North Korea, respectively, and 162-538 deaths were due to domestic emissions. Meeting the air quality guidelines of the WHO could have prevented most of these deaths.

Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation.

Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (n = 23), non-reactivation (n = 24) versus CMV disease (n = 11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells' maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.

Estimation of heat-related deaths during heat wave episodes in South Korea (2006-2017).

In 2016, South Korea experienced extremely high temperatures and the Korea Centre for Disease Control and Prevention (KCDC) reported 17 heat-caused deaths during these heat waves, most due to heat stroke. Because the reported number of heat-caused deaths is only part of the total deaths associated with heat waves, we aimed to estimate attributable deaths during heat wave episodes. We linked mortality to meteorological data in 16 regions in South Korea and estimated relative risk at or above threshold of maximum temperature during summer using generalized linear regression models after controlling for confounders. We computed overall, age-, sex-, and cause-specific attributable deaths from 2006 to 2017. With a 1.5% increase in all-cause mortality per 1 °C increase in concurrent days' maximum temperature during summer, this study estimates a total of 1440 all-cause deaths associated with heat waves during the 2006-2017 study period in South Korea. We estimate that 343 deaths in 2016 can be ascribed to heat waves, which is approximately 20 times more than the number reported by the KCDC (17 heat-caused deaths). This study addresses attributable heat wave deaths in South Korea and illustrates that the reports of medically classified heat-caused deaths seriously underestimate the number of deaths attributable to heat waves. Our findings may enable the implementation and reinforcement of government- and individual-level management strategies for heat waves.

Spatial and Temporal Trends of Number of Deaths Attributable to Ambient PM2.5 in the Korea.

BACKGROUND: We aimed to evaluate the spatial and temporal trends of the health burden attributable to particulate matter less than 2.5 µm in diameter (PM2.5) in the metropolitan cities and provinces of the Korea. METHODS: We used modeled PM2.5 concentration data for the basic administrative levels, comprising the cities and the provinces of Korea, the corresponding annual population census data for each level, and the age and cause specific mortality data. We applied cause-specific integrated exposure-response functions to calculate the premature mortality attributable to ambient PM2.5 for four disease end points (ischemic heart disease [IHD], chronic obstructive pulmonary disease [COPD], lung cancer [LC], and cerebrovascular disease [stroke]) for the year 2015. Moreover, the temporal trends of the health burden from 2006 to 2015 were assessed. RESULTS: The annual average PM2.5 concentration for Korea was 24.4 µg/m3, and 11,924 premature deaths were attributable to PM2.5 exposure in 2015. By simulating the reduction in the annual mean values of PM2.5 to 10 µg/m3, about 8,539 premature deaths were preventable. There was spatial variation in mortality burden attributable to PM2.5 across the sub-national regions of Korea. In particular, the high burden was concentrated at Seoul and Gyeonggi province due to the high population density. However, decreasing trends were noted for most of the metropolitan cities and provinces of Korea since 2006. CONCLUSION: Our findings show that further actions to improve air quality in Korea would substantially improve the health burden due to particulate matter.

Estimation of abnormal temperature effects on elderly mortality in South Korea using the temperature deviation index.

Recent studies have revealed that the effect of temperature on mortality has changed over time. One of the major contributors to the changes is adaptation. We aimed to understand the relationship between elderly mortality and temperature anomaly using the temperature deviation index (TDI), which considers exposure history. Summertime (May to September) mortality data from 1996 to 2014 and meteorological data from 1971 to 2014 were obtained for 16 regions covering South Korea. The TDI was defined as the target day's temperature abnormality compared to previous 25 years' apparent temperature (AT). The relationship between the TDI and elderly mortality for each region was examined by generalized linear modeling with Poisson distribution. Pooled estimates were computed to yield a national effect estimate. Stratified analyses were performed using the percentiles of AT and TDI. Most regions showed positive linear associations, and the associations ranged from 0.4 to 4.3% increase per unit increase of the TDI. In the pooled analyses, a unit increase of the TDI was associated with a 1.4% increase (95% confidence interval [CI] 0.93-1.87) in elderly mortality. In the stratified analysis, the relationship between the TDI and elderly mortality was significant at or above the 75th percentile of AT (1.32% increase; 95% CI 0.47-2.22). We suggest a positive association between the TDI and elderly mortality in South Korea. The association observed particularly in the highest percentile of AT in the stratified analysis suggests independent effects of temperature anomaly in addition to those of absolute AT.

Donor-derived cell-free DNA predicted allograft rejection and severe microvascular inflammation in kidney transplant recipients.

Introduction: The aim of this study is to investigate the clinical validity of donor-derived cell-free DNA (dd-cfDNA) in comparison with that of donor specific anti-HLA antibody (DSA) for predicting biopsy-proven rejection (BPR)and severe microvascular inflammation (severe MVI) in kidney transplant recipients (KTRs). Methods: In this prospective observational investigation, 64 KTRs who underwent the indicated biopsies were included. Blood samples collected prior to biopsy were tested for dd-cfDNA and DSA. Biopsy specimens were classified by a renal pathologist according to the Banff classification. The predictive performance of dd-cfDNA and DSA for histological allograft diagnosis was assessed. Results: KTRs were categorized into the high and low dd-cfDNA groups based on a level of 0.4%. Eighteen patients (28.1%) had positive DSA at biopsy, exhibiting higher dd-cfDNA levels than the DSA-negative patients. BPR and severe MVI incidences were elevated in the high dd-cfDNA group (BPR: 42.9% vs. 3.4%, P <0.001; severe MVI: 37.1% vs. 3.4%, P = 0.001). Also, elevated glomerulitis and MVI scores were observed in the high dd-cfDNA group. DSA showed the highest predictive value for BPR (AUC = 0.880), whereas dd-cfDNA alone excelled in predicting severe MVI (AUC = 0.855). Combination of DSA and dd-cfDNA (>0.4%) yielded sensitivities of 80.0% and 50.0% with specificities of 90.7% and 88.0% for antibody-mediated rejection and severe MVI detection, respectively. Conclusion: The dd-cfDNA test is a predictive tool for BPR and severe MVI, and it can improve the performance, especially when combined with DSA for BPR.

Mortality Burden Due to Short-term Exposure to Fine Particulate Matter in Korea.

OBJECTIVES: Excess mortality associated with long-term exposure to fine particulate matter (PM2.5) has been documented. However, research on the disease burden following short-term exposure is scarce. We investigated the cause-specific mortality burden of short-term exposure to PM2.5 by considering the potential non-linear concentration-response relationship in Korea. METHODS: Daily cause-specific mortality rates and PM2.5 exposure levels from 2010 to 2019 were collected for 8 Korean cities and 9 provinces. A generalized additive mixed model was employed to estimate the non-linear relationship between PM2.5 exposure and cause-specific mortality levels. We assumed no detrimental health effects of PM2.5 concentrations below 15 µg/m3. Overall deaths attributable to short-term PM2.5 exposure were estimated by summing the daily numbers of excess deaths associated with ambient PM2.5 exposure. RESULTS: Of the 2 749 704 recorded deaths, 2 453 686 (89.2%) were non-accidental, 591 267 (21.5%) were cardiovascular, and 141 066 (5.1%) were respiratory in nature. A non-linear relationship was observed between all-cause mortality and exposure to PM2.5 at lag0, whereas linear associations were evident for cause-specific mortalities. Overall, 10 814 all-cause, 7855 non-accidental, 1642 cardiovascular, and 708 respiratory deaths were attributed to short-term exposure to PM2.5. The estimated number of all-cause excess deaths due to short-term PM2.5 exposure in 2019 was 1039 (95% confidence interval, 604 to 1472). CONCLUSIONS: Our findings indicate an association between short-term PM2.5 exposure and various mortality rates (all-cause, non-accidental, cardiovascular, and respiratory) in Korea over the period from 2010 to 2019. Consequently, action plans should be developed to reduce deaths attributable to short-term exposure to PM2.5.

Pretransplant BKV-IgG serostatus and BKV-specific ELISPOT assays to predict BKV infection after kidney transplantation.

Introduction: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection. Methods: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3). BK viremia was diagnosed when blood BKV-DNA of 104 copies/mL or more was detected during follow-up periods. Results: Anti-BKV IgG antibody was detected in 74 (79.6%) of 93 KTRs and in 68 (73.1%) of 93 KT donors. A greater percentage of KTRs who received allograft from donors with high levels of anti-BKV IgG had posttransplant BK viremia (+) than KTRs from donors with low anti-BKV IgG (25.5% [12/47] vs. 4.3% [2/46], respectively; P = 0.007). Pretransplant total BKV-ELISPOT results were lower in BK viremia (+) patients than in patients without viremia (-) 20.5 [range 9.9-63.6] vs. 72.0 [43.2 - 110.8]; P = 0. 027). The sensitivity and specificity of the total BKV-ELISPOT assay (cut-off ≤ 53 spots/3×105 cells) for prediction of posttransplant BK viremia were 71.4 (95% CI: 41.9-91.6) and 54.4 (42.8-65.7), respectively. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results improved specificity to 91.1%. Discussion: Our study highlights the importance of pretransplant BKV-IgG serostatus and BKV-specific CMI in predicting posttransplant BKV infection in KTRs. The combination of high donor BKV-IgG, low recipient BKV-IgG, and low total BKV-ELISPOT results predicted BK viremia after KT. Pretransplant identification of patients at highrisk for BK viremia could enable timely interventions and improve clinical outcomes of KTRs.

Discovery of cellular and genetic signatures of immune tolerance in kidney transplant recipients through single cell RNA sequencing analysis.

The objective of this study was to uncover distinct cellular and genetic signatures of transplant operational tolerance (TOT) in kidney transplant recipients (KTRs) through single cell RNA sequencing (scRNA-seq) using peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from 12 KTRs, including those with TOT (TOT, n = 4), stable allograft function on maintenance immunosuppression (STA, n = 4) and biopsy-proven allograft rejection (BPAR, n = 4). ScRNA-seq of PBMCs was analyzed using 20 cell surface marker antibody sequencing to annotate clusters and 399 immune response panel to identify gene expression. Differences in cellular distribution and gene expression were compared among the three groups. Heatmap hierarchical clustering showed that overall cellular distribution pattern was distinct in TOT in comparison with those in the other two groups, with the proportion of B cells being higher in TOT, attributed to immature B cell fraction (TOT vs. STA vs. BPAR: 4.61% vs. 1.27% vs. 2.53%, p = 0.01). Transcript analysis of B cells revealed that genes involved in allo-immune pathway were downregulated in TOT. In T cell subset analysis, the proportion of naïve T cells and regulatory T cells (Tregs) was increased. In transcript analysis, genes associated with inflammation were decreased, while expression levels of CCR6 in Tregs were increased in TOT. Proportions of NKT and NK cells were increased in TOT than in the other two groups. This study showed that TOT has distinct cellular and genetic signatures such as increases of immature B cells, naïve T cells and Tregs and high expression levels of CCR6 in Tregs.

The influence of HLA A, B, C, DR alleles and HLA haplotypes on cytomegalovirus-specific cell mediated immunity in seropositive Korean kidney transplant candidates.

We evaluated the effect of specific HLA alleles and haplotypes on cytomegalovirus (CMV)-specific cell mediated immunity (CMI) in kidney transplant (KT) candidates. CMV-specific ELISPOT against pp65 and IE-1 antigens (hereafter referred to as pp65 and IE-1, respectively) was performed in 229 seropositive KT candidates. We analyzed the results related to 44 selected HLA alleles (9 HLA-A, 15 HLA-B, 9 HLA-C, and 11 HLA-DR) and 13 HLA haplotypes commonly found in study participants. The pp65 and IE-1 results in 229 seropositive candidates were 227.5 (114.5-471.5) and 41.0 (8.8-185.8) (median [interquartile range]) spots/2 × 105 PBMCs, respectively. The pp65 and IE-1 results showed significant differences between candidates with different HLA alleles (A*02 vs. A*26 [p = 0.016], A*24 vs. A*30 [p = 0.031], B*07 vs. B*46 [p = 0.005], B*54 vs. B*35 [p = 0.041], B*54 vs. B*44 [p = 0.018], B*54 vs. B*51 [p = 0.025], and C*06 vs. C*14 [p = 0.034]). HLA-A*02 and B*54 were associated with increased pp65 and IE-1 results, respectively (p = 0.005 and p < 0.001, respectively). In contrast, the HLA-A*26 and B*46 alleles were associated with a decreased pp65 response, whereas the A*30 allele was associated with a decreased IE-1 response (p < 0.05). The pp65 results correlated with the HLA-A allele frequencies (R = 0.7546, p = 0.019) and the IE-1 results correlated with the HLA-C allele frequencies of the study participants (R = 0.7882, p = 0.012). Among 13 haplotypes, HLA-A*30 ~ B*13 ~ C*06 ~ DRB1*07 showed decreased CMV-CMIs compared to the other HLA haplotypes, probably due to a combination of HLA alleles associated with lower CMV-CMIs. Our results demonstrated that CMV-specific CMIs may be influenced by the HLA allele as well as the HLA haplotype. To better predict CMV reactivation, it is important to estimate risk in the context of HLA allele and haplotype information.

Longitudinal Analysis of SARS-CoV-2-Specific Cellular and Humoral Immune Responses and Breakthrough Infection following BNT162b2/BNT162b2/BNT162b2 and ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naive Healthcare Workers.

Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13-15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate virus neutralization test at nine different time points. Both groups exhibited peak responses one to two months after the second or third dose, followed by gradual declines over six months. Notably, the ChAd group exhibited a gradual increase in ELISPOT results, but their antibody levels declined more rapidly after reaching peak response compared to the BNT group. Six months after the third dose, both groups had substantial cellular responses, with superior humoral responses in the BNT group (p < 0.05). As many as 55 breakthrough infection participants displayed higher neutralization activities against Omicron variants, but similar cellular responses compared to 127 infection-naïve individuals, suggesting cross-immunity. Distinct neutralization classifications (<30%, >80% inhibition) correlated with different ELISPOT results. Our study reveals diverse immune response patterns based on vaccine strategies and breakthrough infections, emphasizing the importance of understanding these dynamics for optimized vaccination decisions.

Effect modification of consecutive high concentration days on the association between fine particulate matter and mortality: a multi-city study in Korea.

OBJECTIVES: Although there is substantial evidence for the short-term effect of fine particulate matter (PM2.5) on daily mortality, few epidemiological studies have explored the effect of prolonged continuous exposure to high concentrations of PM2.5. This study investigated how the magnitude of the mortality effect of PM2.5 exposure is modified by persistent exposure to high PM2.5 concentrations. METHODS: We analyzed data on the daily mortality count, simulated daily PM2.5 level, mean daily temperature, and relative humidity level from 7 metropolitan cities from 2006 to 2019. Generalized additive models (GAMs) with quasi-Poisson distribution and random-effects meta-analyses were used to pool city-specific effects. To investigate the effect modification of continuous exposure to prolonged high concentrations, we applied categorical consecutive-day variables to the GAMs as effect modification terms for PM2.5. RESULTS: The mortality risk increased by 0.33% (95% confidence interval [CI], 0.16 to 0.50), 0.47% (95% CI, -0.09 to 1.04), and 0.26% (95% CI, -0.08 to 0.60) for all-cause, respiratory, and cardiovascular diseases, respectively, with a 10 µg/m3 increase in PM2.5 concentration. The risk of all-cause mortality per 10 µg/m3 increase in PM2.5 on the first and fourth consecutive days significantly increased by 0.63% (95% CI, 0.20 to 1.06) and 0.36% (95% CI, 0.01 to 0.70), respectively. CONCLUSIONS: We found increased risks of all-cause, respiratory, and cardiovascular mortality related to daily PM2.5 exposure on the day when exposure to high PM2.5 concentrations began and when exposure persisted for more than 4 days with concentrations of ≥35 µg/m3. Persistently high PM2.5 exposure had a stronger effect on seniors.

Successful ABO-incompatible living donor kidney transplantation in a recipient who developed flow cytometry crossmatch-positive donor-specific class I HLA antibodies following COVID-19 vaccination.

The effects of COVID-19 vaccination on alloimmunization and clinical impact in transplant candidates remain largely unknown. In a 61-year-old man who had no donor-specific antibodies (DSA) and was planned to undergo ABO-incompatible kidney transplantation (ABOi KT), DSAs (anti-A24, anti-B51, and anti-Cw14) developed after COVID-19 vaccination. After desensitization therapy, antibody level was further increased, leading to flow cytometric crossmatch-positive status. Donor-specific T cell immunity using interferon-gamma ELISPOT was continuously negative, whereas SARS-CoV-2 specific T cell immunity was intact. After confirming the C1q-negative status of DSA, the patient received ABOi KT. The patient had stable graft function and suppressed alloimmunity up to 2 months after KT. COVID-19 vaccination might relate to alloimmunization in transplant candidates, and desensitization through immune monitoring can help guide transplantation.

Long-term exposure to fine particulate matter and incident asthma among elderly adults.

RATIONALE: Although an association of fine particulate matter (PM2.5) with asthma incidence has been assumed, there is insufficient evidence regarding the effect of long-term exposure to PM2.5 on incident asthma among elderly adults. OBJECTIVES: This study aimed to investigate an association between long-term exposure to PM2.5 and incident asthma among elderly adults in South Korea. METHODS: Adults ≥65 years of age (n = 1,220,645) who did not visit hospitals for asthma during a washout period (between 2008 and 2010) were followed up until 2016 using data from the National Health Insurance System in South Korea. Incident asthma was defined as the number of patients with a primary diagnostic code of asthma who visited hospitals more than twice. We linked the health data with district-level PM2.5 concentrations and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for incident asthma after adjusting for potential confounders in time-varying Cox proportional hazard models. MEASUREMENTS AND MAIN RESULTS: Over 5,942,256 person-years, 54,522 patients developed asthma, with an incidence of 9.2 cases/1000 person-years. A 10 µg/m3 increase in the 36-month mean PM2.5 concentration was significantly associated with a 9% increase in incident asthma (HR = 1.09, 95% CI: 1.04-1.14). This association was found to be robust for different definitions of incident asthma and washout periods. CONCLUSION: Long-term exposure to PM2.5 was associated with the incidence of asthma in elderly adults. This finding provides evidence of an association between PM2.5 and adult-onset asthma.

Long-term exposure to moderate fine particulate matter concentrations and cause-specific mortality in an ageing society.

BACKGROUND: Long-term exposure to particulate matter <2.5 µm in size (PM2.5) is considered a risk factor for premature death. However, only a few studies have been conducted in areas with moderate PM2.5 concentrations. Moreover, an ageing society may be more susceptible to environmental exposure and future burden of mortality due to PM2.5. METHODS: This study estimates hazard ratios (HRs) for all-cause and cause-specific mortality from long-term exposure to moderate PM2.5 concentrations in the elderly populations of seven cities in South Korea. We also projected nationwide elderly mortality caused by long-term exposure to PM2.5, accounting for population ageing until 2045. Mortality in 1 720 230 elderly adults aged ≥65 years in 2008 was monitored across 2009-16 and linked to modelled PM2.5 concentrations. RESULTS: A total of 421 100 deaths occurred in 2009-16, and the mean of annual PM2.5 concentration ranged between 21.1 and 31.9 µg/m3 in most regions. The overall HR for a 10 µg/m3 increase in a 36-month PM2.5 moving average was 1.024 (95% confidence intervals: 1.009, 1.039). We estimated that 11 833 all-cause nationwide elderly deaths were attributable to PM2.5 exposure. Annual death tolls may increase to 17 948 by 2045. However, if PM2.5 is reduced to 5 µg/m3 by 2045, the tolls may show a lower increase to 3646. CONCLUSIONS: Long-term exposure to moderately high levels of PM2.5 was associated with increased mortality risk among the elderly. Thus, PM2.5 reduction in response to the projected ageing-associated mortality in South Korea is critical.

Quantitative SARS-CoV-2 Spike Antibody Response in COVID-19 Patients Using Three Fully Automated Immunoassays and a Surrogate Virus Neutralization Test.

Quantitative SARS-CoV-2 antibody assays against the spike (S) protein are useful for monitoring immune response after infection or vaccination. We compared the results of three chemiluminescent immunoassays (CLIAs) (Abbott, Roche, Siemens) and a surrogate virus neutralization test (sVNT, GenScript) using 191 sequential samples from 32 COVID-19 patients. All assays detected >90% of samples collected 14 days after symptom onset (Abbott 97.4%, Roche 96.2%, Siemens 92.3%, and GenScript 96.2%), and overall agreement among the four assays was 91.1% to 96.3%. When we assessed time-course antibody levels, the Abbott and Siemens assays showed higher levels in patients with severe disease (p < 0.05). Antibody levels from the three CLIAs were correlated (r = 0.763-0.885). However, Passing-Bablok regression analysis showed significant proportional differences between assays and converting results to binding antibody units (BAU)/mL still showed substantial bias. CLIAs had good performance in predicting sVNT positivity (Area Under the Curve (AUC), 0.959-0.987), with Abbott having the highest AUC value (p < 0.05). SARS-CoV-2 S protein antibody levels as assessed by the CLIAs were not interchangeable, but showed reliable performance for predicting sVNT results. Further standardization and harmonization of immunoassays might be helpful in monitoring immune status after COVID-19 infection or vaccination.