1.Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study
Sung Hye KONG ; Ae Jeong JO ; Chan Mi PARK ; Kyun Ik PARK ; Ji Eun YUN ; Jung Hee KIM
Endocrinology and Metabolism 2025;40(1):82-92
Background:
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods:
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results:
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.
2.Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain
Sung Bum PARK ; Jeong Hyeon JO ; Seong Soon KIM ; Won Hoon JUNG ; Myung-Ae BAE ; Byumseok KOH ; Ki Young KIM
Biomolecules & Therapeutics 2025;33(3):447-457
Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.
3.Prognostic Value of Ambulatory Status at Transplant in Older Heart Transplant Recipients: Implications for Organ Allocation Policy
Junho HYUN ; Jong-Chan YOUN ; Jung Ae HONG ; Darae KIM ; Jae-Joong KIM ; Myoung Soo KIM ; Jaewon OH ; Jin-Jin KIM ; Mi-Hyang JUNG ; In-Cheol KIM ; Sang-Eun LEE ; Jin Joo PARK ; Min-Seok KIM ; Sung-Ho JUNG ; Hyun-Jai CHO ; Hae-Young LEE ; Seok-Min KANG ; Dong-Ju CHOI ; Jon A. KOBASHIGAWA ; Josef STEHLIK ; Jin-Oh CHOI
Journal of Korean Medical Science 2025;40(3):e14-
Background:
Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort.
Methods:
We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation.
Results:
Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465).
Conclusion
Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.
4.Prognostic Value of Ambulatory Status at Transplant in Older Heart Transplant Recipients: Implications for Organ Allocation Policy
Junho HYUN ; Jong-Chan YOUN ; Jung Ae HONG ; Darae KIM ; Jae-Joong KIM ; Myoung Soo KIM ; Jaewon OH ; Jin-Jin KIM ; Mi-Hyang JUNG ; In-Cheol KIM ; Sang-Eun LEE ; Jin Joo PARK ; Min-Seok KIM ; Sung-Ho JUNG ; Hyun-Jai CHO ; Hae-Young LEE ; Seok-Min KANG ; Dong-Ju CHOI ; Jon A. KOBASHIGAWA ; Josef STEHLIK ; Jin-Oh CHOI
Journal of Korean Medical Science 2025;40(3):e14-
Background:
Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort.
Methods:
We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation.
Results:
Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465).
Conclusion
Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.
5.Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study
Sung Hye KONG ; Ae Jeong JO ; Chan Mi PARK ; Kyun Ik PARK ; Ji Eun YUN ; Jung Hee KIM
Endocrinology and Metabolism 2025;40(1):82-92
Background:
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods:
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results:
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.
6.Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain
Sung Bum PARK ; Jeong Hyeon JO ; Seong Soon KIM ; Won Hoon JUNG ; Myung-Ae BAE ; Byumseok KOH ; Ki Young KIM
Biomolecules & Therapeutics 2025;33(3):447-457
Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.
7.Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study
Sung Hye KONG ; Ae Jeong JO ; Chan Mi PARK ; Kyun Ik PARK ; Ji Eun YUN ; Jung Hee KIM
Endocrinology and Metabolism 2025;40(1):82-92
Background:
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods:
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results:
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.
8.Prognostic Value of Ambulatory Status at Transplant in Older Heart Transplant Recipients: Implications for Organ Allocation Policy
Junho HYUN ; Jong-Chan YOUN ; Jung Ae HONG ; Darae KIM ; Jae-Joong KIM ; Myoung Soo KIM ; Jaewon OH ; Jin-Jin KIM ; Mi-Hyang JUNG ; In-Cheol KIM ; Sang-Eun LEE ; Jin Joo PARK ; Min-Seok KIM ; Sung-Ho JUNG ; Hyun-Jai CHO ; Hae-Young LEE ; Seok-Min KANG ; Dong-Ju CHOI ; Jon A. KOBASHIGAWA ; Josef STEHLIK ; Jin-Oh CHOI
Journal of Korean Medical Science 2025;40(3):e14-
Background:
Shortage of organ donors in the Republic of Korea has become a major problem. To address this, it has been questioned whether heart transplant (HTx) allocation should be modified to reduce priority of older patients. We aimed to evaluate post-HTx outcomes according to recipient age and specific pre-HTx conditions using a nationwide prospective cohort.
Methods:
We analyzed clinical characteristics of 628 patients from the Korean Organ Transplant Registry who received HTx from January 2015 to December 2020. Enrolled recipients were divided into three groups according to age. We also included comorbidities including ambulatory status. Non-ambulatory status was defined as pre-HTx support with either extracorporeal membrane oxygenation, continuous renal replacement therapy, or mechanical ventilation.
Results:
Of the 628 patients, 195 were < 50 years, 322 were 50–64 years and 111 were ≥ 65years at transplant. Four hundred nine (65.1%) were ambulatory and 219 (34.9%) were nonambulatory. Older recipients tended to have more comorbidities, ischemic cardiomyopathy, and received older donors. Post-HTx survival was significantly lower in older recipients (P = 0.025) and recipients with non-ambulatory status (P < 0.001). However, in contrast to non-ambulatory recipients who showed significant survival differences according to the recipient’s age (P = 0.004), ambulatory recipients showed comparable outcomes (P = 0.465).
Conclusion
Our results do not support use of age alone as an allocation criterion. Transplant candidate age in combination with some comorbidities such as non-ambulatory status may identify patients at a sufficiently elevated risk at which suitability of HTx should be reconsidered.
9.Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain
Sung Bum PARK ; Jeong Hyeon JO ; Seong Soon KIM ; Won Hoon JUNG ; Myung-Ae BAE ; Byumseok KOH ; Ki Young KIM
Biomolecules & Therapeutics 2025;33(3):447-457
Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression.In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.
10.Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study
Sung Hye KONG ; Ae Jeong JO ; Chan Mi PARK ; Kyun Ik PARK ; Ji Eun YUN ; Jung Hee KIM
Endocrinology and Metabolism 2025;40(1):82-92
Background:
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods:
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results:
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

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