https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/334 2026-04-04T11:53:23Z 2026-04-04T11:53:23Z Jung, Jiyoung Lee, Kiwook Song, Catherine Park, Jong Sun Kwon, Byoung Soo Kim, Min-Hye Kim, Byung-Keun Lee, Sang Min Yang, Min-Suk https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64172 2023-12-13T11:31:13Z 20230609-01-01T00:00:00Z

Title: Exploration of Cough Counts and Epochs in Patients with Asthma and Interstitial Lung Disease Authors: Jung, Jiyoung; Lee, Kiwook; Song, Catherine; Park, Jong Sun; Kwon, Byoung Soo; Kim, Min-Hye; Kim, Byung-Keun; Lee, Sang Min; Yang, Min-Suk Abstract: Background: Cough counts are widely used for cough studies in patients with various respiratory diseases. The cough epoch is a cluster of cough counts,1 which may reveal the severity of coughs and cough patterns that are indiscernible with cough count alone. Despite its potential clinical importance, cough epochs are not as commonly investigated. One of the few previous studies was conducted on the nighttime cough epoch focused on COPD patients.2 In this study, we observed both the cough counts and cough epochs in patients with asthma and interstitial lung disease (ILD). Methods: In order to observe the cough epochs in respiratory patients, we retrospectively analyzed the data from two independent clinical studies. Cough sounds were recorded from 21 ILD patients recruited in Seoul National University Bundang Hospital and from 24 patients with asthma exacerbation recruited in 7 academic medical centers in South Korea. The ILD patients recorded coughs for 5 consecutive days on two occasions separated by a 3-month period (10 total days), and the asthmatic patients recorded coughs for 7 consecutive days. Both groups recorded for 2 h in awake time and 5 h in sleep time daily, and they received the standard treatment throughout the study. Cough events from recordings were detected by the Coughy AI algorithm,2 and the cough epochs were calculated by counting the number of continuous coughing sounds without a 2-s pause as defined in Morice et al.1 Finally, the trends of cough and epoch frequency over days were compared in each study group. Results: The cough frequency and the epoch frequency both decreased over the course of treatment in awake and sleep time for patients with asthma exacerbation as shown in Fig. 1(a) and (c). The correlation between the cough frequency and epoch frequency was high with R2 of 0.986 and 0.949, respectively. However, in ILD patients, two cough measures didn’t show a decreasing trend clearly nor moved together over days with no clear correlation (R2) of 0.125 in awake time and 0.521 in sleep time (Fig. 1(b) and (d)). Conclusion: We have observed the trend of cough and epoch frequency over time and how they are correlated. Based on our study, the two cough measures showed different trends over the course of treatment in patients with asthma and ILD. A larger population study will be needed to pursue these initial observations and find a clinical role of the cough epoch for respiratory patients.

20230609-01-01T00:00:00Z Anh, N. Tung, P. Jang, T. Min, J. Kim, J. Oh, J. Lee, H. Lee, H. Kim, H. Park, H. Lee, H. Park, I. Mok, J. Lee, J. Ahn, S. Long, N. Cho, Y. Shin, J. https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63752 2023-12-13T11:31:01Z 20230324-01-01T00:00:00Z

Title: METABOLIC PROFILE INVESTIGATION REVEALS WIDE VARIABILITY IN THE EXPOSURE OF ISONIAZID AND ITS HEPATOTOXIC METABOLITES IN TUBERCULOSIS PATIENTS Authors: Anh, N.; Tung, P.; Jang, T.; Min, J.; Kim, J.; Oh, J.; Lee, H.; Lee, H.; Kim, H.; Park, H.; Lee, H.; Park, I.; Mok, J.; Lee, J.; Ahn, S.; Long, N.; Cho, Y.; Shin, J. Abstract: Background Isoniazid (INH) is a first‐line agent for the treatment of tuberculosis (TB), a global health crisis. INH and its metabolites exposure variability could influence the effectiveness and toxicity of INH‐based therapy. To assess the interindividual differences in INH metabolism and distribution we investigated the impact of clinical and pharmacogenetic factors on the metabolic profiles of the drug. Methods A targeted profiling of INH and its four major metabolites (i.e., acetylisoniazid, isonicotinic acid, hydrazine, and acetylhydrazine) in plasma of 965 TB patient was performed using liquid chromatography–tandem mass spectrometry. N‐acetyltransferase 2 (NAT2) genotypes were also determined for patients’ acetylator phenotypes. After removing non‐compliance subjects, 876 TB patients’ INH metabolic profiles, including 345 rapid, 412 intermediate and 119 slow acetylator, were selected for subsequent analyses. The distribution of INH and its metabolites was examined during 24 hour time‐course to characterize their exposure variabilities in different acetylators and clinical factors. Results The median concentration of INH in its time‐course was 2.5‐ fold and 1.8‐ fold higher in slow acetylator compared to rapid and intermediate acetylator, respectively. Median concentrations of hydrazine, the hepatotoxic metabolite, were over 1.7‐ fold higher in slow acetylator compared to other NAT2 phenotypes. The meta-bolic ratio distribution of INH was significantly associated with NAT2 phenotypes. Conclusion INH metabolic profiles are markedly associated with acetyl-ator phenotypes of TB patients. Our findings provide a proof of concept towards implementing an acetylator phenotype‐based dosing for a safe and effective INH‐ based therapy.

20230324-01-01T00:00:00Z Kim, R. Jayanti, R. Jang, T. Min, J. Kim, J. Oh, J. Lee, H. Lee, H. Shin, K. Kang, B. Kim, H. Ko, Y. Kim, J. Choi, Y. Nguyen, P. Cho, Y. Shin, J. https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63753 2023-12-13T11:31:01Z 20230323-01-01T00:00:00Z

Title: DEVELOPMENT OF POPULATION PHARMACOKINETICS MODEL OF PYRAZINAMIDE AND OPTIMAL DOSE RECOMMENDATION FOR ELDERLY WITH DIABETES MELLITUS IN KOREAN TUBERCULOSIS PATIENTS Authors: Kim, R.; Jayanti, R.; Jang, T.; Min, J.; Kim, J.; Oh, J.; Lee, H.; Lee, H.; Shin, K.; Kang, B.; Kim, H.; Ko, Y.; Kim, J.; Choi, Y.; Nguyen, P.; Cho, Y.; Shin, J. Abstract: Background Diabetes mellitus (DM) is common comorbidity that ap-peared among the elderly population, likely to complicate their clinical conditions. The effect of DM on the pharmacokinetics (PK) of anti‐tuberculosis (TB) drugs remained arguable. However, DM potentially hampered successful TB treatment. Through the development of the population PK model, we aimed to provide op-timal dosing of pyrazinamide (PZA) for the geriatric DM population with TB in regard to the probability of achieving the PK target. Methods PZA concentrations at random post‐dose points, demographic characteristics, and clinical information were collected in a multicenter prospective cohort study from 13 hospitals in Korea. Population PK model was developed using a non‐linear mixed effect method and dose simulation was carried out. Data from 610 TB patients were divided into a training and test dataset with a 4 to 1 ratio. Results A one‐compartment model with allometric scaling for body size effect adequately described PK parameters of PZA. Geriatric patients (> 70 years old) with DM were found as significant covariates, increasing the apparent clear-ance (CL/F) of PZA by 30% (CL/F: 4.49 L/h). Our model was externally evaluated using the test set and provided better predictive performance compared to the previously published model. Following our simulations to assess efficacy and toxicity, geriatric DM patients with TB required higher doses of PZA in order to achieve the area under concentration from 0 to 24 hours (AUC0‐ 24) target of ≥363 mg/h/L. Conclusion The established population PK model sufficiently described the PK parameters of PZA in Korean TB patients. Our model can be useful in therapeutic drug monitoring to suggest the optimal dose of PZA, particularly for the geriatric DM population with TB.EP‐ 014.

20230323-01-01T00:00:00Z Kim, Taeyun Jang, Tae Won Choi, Chang Min Kim, Mi-Hyun Lee, Sung Yong Chang, Yoon Soo Lee, Kye Young Kim, Seung Joon Yang, Sei Hoon Ryu, Jeong Seon Lee, Jeong Eun Lee, Shin Yup Park, Chan Kwon Lee, Sang Hoon Jang, Seung Hun Yoon, Seong Hoon Oh, Hyung-Joo https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/64379 2024-07-11T11:00:53Z 2023-10-01T00:00:00Z

Title: Final Report on Real-World Effectiveness of Sequential Afatinib and Osimertinib in EGFR-Positive Advanced Non-Small Cell Lung Cancer: Updated Analysis of the RESET Study Authors: Kim, Taeyun; Jang, Tae Won; Choi, Chang Min; Kim, Mi-Hyun; Lee, Sung Yong; Chang, Yoon Soo; Lee, Kye Young; Kim, Seung Joon; Yang, Sei Hoon; Ryu, Jeong Seon; Lee, Jeong Eun; Lee, Shin Yup; Park, Chan Kwon; Lee, Sang Hoon; Jang, Seung Hun; Yoon, Seong Hoon; Oh, Hyung-Joo Abstract: Purpose This study aimed to report the final analysis of time-on-treatment (TOT) and overall survival (OS) in patients with advanced -stage epidermal growth factor receptor (EGFR)+ non-small cell lung cancer (NSCLC) who received sequential afatinib and osimertinib and to compare the outcomes with other second-line regimens (comparator group).Materials and Methods In this updated report, the existing medical records were reviewed and rechecked. TOT and OS were updated and analyzed according to clinical features using the Kaplan-Meier method and log-rank test. TOT and OS were compared with those of the comparator group, in which most patients received pemetrexed-based treatments. A multivariable Cox proportional hazard model was used to evaluate features that could affect survival outcomes.Results The median observation time was 31.0 months. The follow-up period was extended to 20 months. A total of 401 patients who received first-line afatinib were analyzed (166 with T790M+ and second-line osimertinib, and 235 with unproven T790M and other second-line agents). Median TOTs on afatinib and osimertinib were 15.0 months (95% confidence interval [CI], 14.0 to 16.1) and 11.9 months (95% CI, 8.9 to 14.6), respectively. The median OS in the osimertinib group was 54.3 months (95% CI, 46.7 to 61.9), much longer than that in the comparator group. In patients who received osimertinib, the OS was longest with Del19+ (median, 59.1; 95% CI, 48.7 to 69.5).Conclusion This is one of the largest real-world studies reporting the encouraging activity of sequential afatinib and osimertinib in Asian patients with EGFR+ NSCLC who acquired the T790M mutation, particularly Del19+.

2023-10-01T00:00:00Z