Slow gut transit increases the risk of Alzheimer’s disease: an integrated study of the bi-national cohort in South Korea and Japan and Alzheimer’s disease model mice

IntroductionAlthough the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown.ObjectivesTo investigate the potential association between slow gut transit and AD using epidemiological data and a murine model.MethodsWe conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009–2010) and the follow-up period (2011–2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests.ResultsConstipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01–2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61–3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aβ and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue.ConclusionImpaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted.</p

Incident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK

As mounting evidence suggests a higher incidence of adverse consequences, such as disruption of the immune system, among patients with a history of COVID-19, we aimed to investigate post-COVID-19 conditions on a comprehensive set of allergic diseases including asthma, allergic rhinitis, atopic dermatitis, and food allergy. We used nationwide claims-based cohorts in South Korea (K-CoV-N; n = 836,164; main cohort) and Japan (JMDC; n = 2,541,021; replication cohort A) and the UK Biobank cohort (UKB; n = 325,843; replication cohort B) after 1:5 propensity score matching. Among the 836,164 individuals in the main cohort (mean age, 50.25 years [SD, 13.86]; 372,914 [44.6%] women), 147,824 were infected with SARS-CoV-2 during the follow-up period (2020−2021). The risk of developing allergic diseases, beyond the first 30 days of diagnosis of COVID-19, significantly increased (HR, 1.20; 95% CI, 1.13−1.27), notably in asthma (HR, 2.25; 95% CI, 1.80−2.83) and allergic rhinitis (HR, 1.23; 95% CI, 1.15−1.32). This risk gradually decreased over time, but it persisted throughout the follow-up period (≥6 months). In addition, the risk increased with increasing severity of COVID-19. Notably, COVID-19 vaccination of at least two doses had a protective effect against subsequent allergic diseases (HR, 0.81; 95% CI, 0.68−0.96). Similar findings were reported in the replication cohorts A and B. Although the potential for misclassification of pre-existing allergic conditions as incident diseases remains a limitation, ethnic diversity for evidence of incident allergic diseases in post-COVID-19 condition has been validated by utilizing multinational and independent population-based cohorts.</p

National trends and prevalence of atopic dermatitis and pandemic-related factors among Korean adults, 2007-2021

Introduction: Previous studies have variably reported inconclusive trends in the prevalence of atopic dermatitis (AD) among adults, and there are limited data on the impact of the COVID-19 pandemic. We aimed to investigate the national trends and age-stratified prevalence of AD among adults from 2007 to 2021 in South Korea, focusing mainly on the impact of the COVID-19 pandemic-related factors. Methods: A nationwide cross-sectional study was conducted using the Korea National Health and Nutrition Examination Survey data from 2007 to 2021. Overall and age-stratified prevalence for AD were assessed using weighted beta coefficients or odds ratios. Results: A total of 83,566 adults over 20 years (male, 49.40%) were included. During the observation period, the prevalence of AD was stable in the overall population from 2.61% (95% CI, 2.29–2.93) in 2007–2009 to 2.15% (1.68–2.63) in 2020 and 2.38% (1.81–2.95) in 2021. However, the weighted prevalence of AD in adults aged 40–59 years old decreased during the pre-pandemic era, and the prevalence of AD in adults aged above 60 years significantly decreased during the pandemic, with a significant decline observed after the initial outbreak. From age-stratification analysis, the adults aged 40–59 years showed a significant increase after the pandemic outbreak which was evident in specific variables: individuals with rural residence, lower education, and lower household income quartiles. Adults aged above 60 years showed a significant decrease in the slope after the outbreak, evident in specific variables: individuals of female, rural residence, lower education, and lower household income quartiles. Conclusion: We observed a stable overall prevalence of AD throughout the 15-year observation period. However, the age-stratified analysis suggested significantly different trends according to age-stratified groups and the impact of the COVID-19 pandemic on the prevalence of AD.</p

National trends in asthma prevalence in South Korea before and during the COVID-19 pandemic 1998-2021

To the Editor,Since the COVID-19 pandemic has a drastic effect on diverse allergic diseases, research on the critical impact of COVID-19 on asthma has been highlighted internationally. According to previous studies, the prevalence of asthma increased worldwide over the past decades due to pandemic.1, 2 However, previous studies reported in South Korea have conflicting evidence on whether the prevalence of asthma has decreased or increased, especially among adolescents.3 Thus, to further understand the context of this extraordinary trend, we examined the trends of age-stratified asthma prevalence in South Koreans before and during the COVID-19 pandemic.4 The effects of age and other socioeconomic and environmental variables on these trends were analysed using data collected from the Korean National Health and Nutrition Examination Survey (KNHANES), 1998–2021.5 An annual survey conducted by the Korea Disease Control and Prevention Agency (KDCA), 1998–2021...</p

National trends in sleep sufficiency and sleep time among adolescents, including the late-COVID-19 pandemic, 2009-2022: a nationally representative serial study in South Korea

South Korea has garnered a reputation for its high prevalence of sleep deprivation among adolescents (Choi et al., 2022). Given the profound health implications of sleep deprivation (Li et al., 2023; Ramar et al., 2021), the significance of sufficient sleep, especially among adolescents, cannot be overstressed. Recognizing these potential health ramifications among the population, the American Academy of Sleep Medicine (AASM) and the U.S. Centers for Disease Control and Prevention (CDC)’s Morbidity and Mortality Weekly Report (MMWR) have produced recommendations for sleep time in adolescents; both organizations have recommended adolescents to have eight to ten hours of sleep a day (Wheaton et al., 2018). With South Korea’s pre-existing challenges regarding adolescent sleep, understanding the potential compounded effects of the pandemic is crucial; by conducting this cross sectional, comprehensive analysis, it would be possible to derive actional insights to mitigate the negative impacts and promote healthier sleep behaviors amongst South Korean adolescents.</p

National trends in depression and suicide attempts and COVID-19 pandemic-related factors, 1998-2021: a nationwide study in South Korea

Background: Despite the significant psychiatric effects of the COVID-19 pandemic, there’s limited data on the prevalence and risk factors of depression and suicide attempts among South Korean adults.Methods: A nationwide cross-sectional study using the Korea National Health and Nutrition Examination Survey (KNHANES) data from 1998 to 2021 was conducted. Changes in prevalence and risk factors for depression and suicide attempts were assessed using weighted odds ratios or weighted beta coefficients.Results: During the observation period (1998–2021), the prevalence of depression increased in the overall population; however, no significant surge was found regarding the COVID-19 pandemic, from 2.78% (95% CI, 2.41–3.15) in 1998–2005–4.96% (4.32–5.61) in 2020 and 5.06% (4.43–5.69) in 2021. However, immediately after the onset of the pandemic, younger ages, male sex, urban residence, higher education, and high economic status became significant vulnerable factors compared to pre-pandemic periods. The prevalence of suicide attempts remained stable, and there was no notable surge specifically related to the COVID-19 pandemic, from 0.23% (95% CI, 0.18–0.28) in 1998–2005–0.45% (0.25–0.66) in 2020 and 0.42% (0.24–0.60) in 2021. Furthermore, no distinct vulnerable factors associated with suicide attempts have been identified.</p

Trends in hypertension prevalence, awareness, treatment, and control in South Korea, 1998-2021: a nationally representative serial study

The impact of the pandemic on hypertension management is unknown, particularly regarding changes in demographic risk factors. We conducted a comprehensive study between 1998 and 2021 on the long-term trends in hypertension prevalence in South Korea, including a comparison of the pre-pandemic and pandemic eras. Data from 1998 to 2021 of 108,687 Korean adults were obtained through a nationwide, large-scale, and serial study. We conducted a weighted complex sampling analysis on the estimates of national prevalence and compared the slope of hypertension prevalence before and during the pandemic to determine the trend dynamics. We included 108,687 participants over 24 years, 1998–2021. While the prevalence of patients with hypertension consistently increased before the pandemic from 25.51% [95% CI: 24.27–26.75] in 1998–2005 to 27.81% [95% CI: 26.97– 28.66] in 2016–2019, the increasing slope in hypertension prevalence slowed during the pandemic period (28.07% [95% CI: 26.16–29.98] for 2021; βdif, −0.012 [−0.023 to 0.000]). Hypertension awareness, treatment, control, and control rates among patients receiving treatment followed similar trends. Compared to the pre-pandemic era, individuals aged 19–59 years or male had signifcantly increased control rates among the treated patients during the pandemic. This study investigated longterm trends in hypertension prevalence, awareness, treatment, and control among Korean adults. The absence of a reduction in the health indicators associated with hypertension during the pandemic implies that medical services for individuals with hypertension remain unafected.</p

National trends in allergic rhinitis and chronic rhinosinusitis and COVID-19 pandemic related factors in South Korea, from 1998 to 2021

Introduction: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. Method: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained β-coefficients with 95% confidence intervals (CI). Results: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57–6.10) in 1998–2005 to 8.99% (8.09–9.91) in 2021 and CRS from 1.84% (1.70–1.97) in 1998–2005 to 3.70% (3.18–4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. Conclusions: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.</p

Prenatal and postnatal exposure to antibiotics and risk of food allergy in the offspring: a nationwide birth cohort study in South Korea

Background: There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. Methods: Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n= 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity-matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses.Results: During the follow-up period (median 6.92 years [IQR, 4.72–9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04–1.09] and postnatal [HR, 1.05; 95% CI, 1.01–1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester-specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. 2 of 12 | OH et al. 1 | INTRODUCTION Food allergy is a serious health concern across the globe, especially among children.1 Recent studies from the United States have reported that the prevalence of food allergy among children reached 7.6%2 and continued to grow rapidly due to urbanization and westernization.1 Food allergy can induce life-threatening anaphylaxis and cause significant morbidity and mortality.1 Several genetic and environmental factors have been reported to lead to a lack or loss of tolerance to specific foods3–5 thereby resulting in the development of food allergy. In murine models, the gut microbiome performs critical functions in the development of immune tolerance to food allergens.6 Further, it is well-established that the gut microbiome can be perturbed by numerous factors including antibiotic treatment.7 The administration of antibiotics during pregnancy and young infancy is become increasingly prevalent and antibiotics account for ~30% and ~80% of total prescribed medications dispensed to preschool children and pregnant women, respectively.8 At the same time, mounting evidence suggests that prenatal exposure to antibiotics may increase the risk of chronic diseases including asthma9–14 and atopic dermatitis.15 However, only one study has investigated the association between early antibiotic exposure and childhood food allergy at the population level.16 This previous study has several limitations: not taking the potential confounding factors (e.g., familial history of allergic diseases and maternal smoking status) into consideration and only examining postnatal exposure to antibiotics; therefore, excluding prenatal exposure to antibiotics. Detailing the relationship between maternal antibiotic use and the risk of food allergy in the offspring has clinical and scientific significance ascribed to the fact that maternal antibiotic use in pregnancy may make adverse modifications to the microbiome, resulting in the development of food allergy in offspring. Thus, we designed and executed four different cohorts within the same population, using International Classification of Diseases, 10th edition (ICD-10) codes, and predetermined criteria for both maternal antibiotics and food allergy in offspring to control for a great number of potential confounders using nationwide birth cohort study in South Korea. We aimed to understand the potential association of fetal and postnatal antibiotic exposure on the development of food allergies among children. 2 | METHODS 2.1 | Data source A large-scale population-based birth cohort of the National Health Insurance Service (NHIS) in South Korea was conducted in this study.17–19 We established a mother–child paired birth cohort among all infants born between January 1, 2010, and December 31, 2017. We used a unique insurance identification number shared within a family to construe the mother–child pairs.20 South Korea has a national health insurance that covers approximately 98% of all Korean citizens and the Korean government provides the first general health examination to all infants aged 6 months.20 The government anonymized all patient-related data to robust confidentiality. A previous study indicated that the overall positive predictive value for diagnostic records of the NHIS data was 82%.21 This study was approved by the Institutional Review Board of Kyung Hee University (KHSIRB-23-241(EA)). The requirement for informed consent was waived as this study used de-identified administrative data. 2.2 | Study design and participants: (1) full unmatched cohort; (2) Propensity score-matched cohort; (3) health-screening cohort; and (4) sibling cohort We set the “index date” as the birth date of each child. The followup ended on December 31, 2020, on the date of the first diagnosis of food allergy, or at the death of a child, whichever happened first. The observation period was between January 1, 2009, and December 31, 2020 (Figure S1). Among the mother–child pairs enrolled from 2009Conclusion: This study reported a moderate association between early-life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods.</p

National prevalence of smoking among adolescents at tobacco tax increase and COVID-19 pandemic in South Korea, 2005-2022

Prior research has predominantly focused on the overall effects of the tobacco tax increase and the COVID-19 pandemic on adolescent smoking behavior. However, there is a need to examine both the immediate and sustained associations of these two factors on subgroups of adolescents, employing an interrupted time-series model. We aimed to investigate the immediate and sustained association of tobacco tax increase and the COVID-19 pandemic on adolescent smoking prevalence. This study utilized data from the Korea Youth Risk Behavior Web-Based Survey to analyze the prevalence of current smoking among all participants (CSP) and the prevalence of daily smoking among current smokers (DSP) of Korean adolescents (n = 1,159,995; mean, age 14.99; male 51.5%) over 18 years from 2005 to 2022. The study examined 18-year trends in CSP and DSP among Korean adolescents, emphasizing the influences of the 2015 tobacco tax increase and the COVID-19 pandemic, using β coefficients and their differences (βdiff) from an interrupted time-series ARIMA model. While CSP exhibited a decreasing trend, DSP exhibited an increasing trend. Tobacco tax increase was associated with both the short and long terms in smoking prevalence, however, the short-term association on prevalence (CSP, − 3.076 [95% CI, − 3.707 to − 2.445]; DSP, − 4.112 [95% CI, − 6.488 to − 1.735]) was stronger. The pandemic was associated with an immediate increase in DSP (9.345 [95% CI, 5.285–13.406]). These effects were strongest among adolescents from low economic status and those exposed to familial secondhand smoking. Supportive programs for adolescents in low-income families will help overcome the effects associated with the pandemic. As a tobacco tax increase was associated with a reduction in smoking prevalence, this could be one method to overcome the effects of the pandemic.</p