1.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
2.2025 Seoul Consensus on Clinical Practice Guidelines for Irritable Bowel Syndrome
Yonghoon CHOI ; Young Hoon YOUN ; Seung Joo KANG ; Jeong Eun SHIN ; Young Sin CHO ; Yoon Suk JUNG ; Seung Yong SHIN ; Cheal Wung HUH ; Yoo Jin LEE ; Hoon Sup KOO ; Kwangwoo NAM ; Hong Sub LEE ; Dong Hyun KIM ; Ye Hyun PARK ; Min Cheol KIM ; Hyo Yeop SONG ; Sung-Hoon YOON ; Sang Yeol LEE ; Miyoung CHOI ; Moo-In PARK ; In-Kyung SUNG ;
Journal of Neurogastroenterology and Motility 2025;31(2):133-169
Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.
3.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
4.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
5.2025 Seoul Consensus on Clinical Practice Guidelines for Irritable Bowel Syndrome
Yonghoon CHOI ; Young Hoon YOUN ; Seung Joo KANG ; Jeong Eun SHIN ; Young Sin CHO ; Yoon Suk JUNG ; Seung Yong SHIN ; Cheal Wung HUH ; Yoo Jin LEE ; Hoon Sup KOO ; Kwangwoo NAM ; Hong Sub LEE ; Dong Hyun KIM ; Ye Hyun PARK ; Min Cheol KIM ; Hyo Yeop SONG ; Sung-Hoon YOON ; Sang Yeol LEE ; Miyoung CHOI ; Moo-In PARK ; In-Kyung SUNG ;
Journal of Neurogastroenterology and Motility 2025;31(2):133-169
Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.
6.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
7.2025 Seoul Consensus on Clinical Practice Guidelines for Irritable Bowel Syndrome
Yonghoon CHOI ; Young Hoon YOUN ; Seung Joo KANG ; Jeong Eun SHIN ; Young Sin CHO ; Yoon Suk JUNG ; Seung Yong SHIN ; Cheal Wung HUH ; Yoo Jin LEE ; Hoon Sup KOO ; Kwangwoo NAM ; Hong Sub LEE ; Dong Hyun KIM ; Ye Hyun PARK ; Min Cheol KIM ; Hyo Yeop SONG ; Sung-Hoon YOON ; Sang Yeol LEE ; Miyoung CHOI ; Moo-In PARK ; In-Kyung SUNG ;
Journal of Neurogastroenterology and Motility 2025;31(2):133-169
Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.
8.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
9.Trends and Clinical Characteristics of Next-Generation Sequencing–Based Genetic Panel Tests: An Analysis of Korean Nationwide Claims Data
Mi JANG ; Hae Yong PAK ; Ja Yoon HEO ; Hyunsun LIM ; Yoon-La CHOI ; Hyo Sup SHIM ; Eun Kyung KIM
Cancer Research and Treatment 2024;56(1):27-36
Purpose:
In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea.
Materials and Methods:
This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs.
Results:
Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020.
Conclusion
This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.
10.Clinical Impact of Genomic and Pathway Alterations in Stage I EGFR-Mutant Lung Adenocarcinoma
Jae Seok LEE ; Eun Kyung KIM ; Kyung A KIM ; Hyo Sup SHIM
Cancer Research and Treatment 2024;56(1):104-114
Purpose:
We investigated the clinical impact of genomic and pathway alterations in stage I epidermal growth factor receptor (EGFR)–mutant lung adenocarcinomas, which have a high recurrence rate despite complete surgical resection.
Materials and Methods:
Out of the initial cohort of 257 patients with completely resected stage I EGFR-mutant lung adenocarcinoma, tumor samples from 105 patients were subjected to analysis using large-panel next-generation sequencing. We analyzed 11 canonical oncogenic pathways and determined the number of pathway alterations (NPA). Survival analyses were performed based on co-occurring alterations and NPA in three patient groups: all patients, patients with International Association for the Study of Lung Cancer (IASLC) pathology grade 2, and patients with recurrent tumors treated with EGFR–tyrosine kinase inhibitor (TKI).
Results:
In the univariate analysis, pathological stage, IASLC grade, TP53 mutation, NPA, phosphoinositide 3-kinase pathway, p53 pathway, and cell cycle pathway exhibited significant associations with worse recurrence-free survival (RFS). Moreover, RPS6KB1 or EGFR amplifications were linked to a poorer RFS. Multivariate analysis revealed that pathologic stage, IASLC grade, and cell cycle pathway alteration were independent poor prognostic factors for RFS (p=0.002, p < 0.001, and p=0.006, respectively). In the grade 2 subgroup, higher NPA was independently associated with worse RFS (p=0.003). Additionally, in patients with recurrence treated with EGFR-TKIs, co-occurring TP53 mutations were linked to shorter progression-free survival (p=0.025).
Conclusion
Genomic and pathway alterations, particularly cell cycle alterations, high NPA, and TP53 mutations, were associated with worse clinical outcomes in stage I EGFR-mutant lung adenocarcinoma. These findings may have implications for risk stratification and the development of new therapeutic strategies in early-stage EGFR-mutant lung cancer patients.

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