Ozone induced airway inflammation in Transgenerational mice

배다정,이현주,이종욱,장헌수,박종숙,박춘식 대한결핵 및 호흡기학회 2015 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.120 No.-

ROS could cause changes of epigenetics. The object of the study is to investigate the influence of ozone exposure in parent generation (F0) on the phenotype of offspring (~F3). Six-weeks old pregnant BALB/C female mice (F0) were exposed to O3 (1ppm; Ozone-F0) or filtered air (Air-F0) until the next generation (F1) is born. F1 generation mice were exposed to air for 6weeks after birth and then the airway resistance and differential cell counts in bronchial alveolar lavage fluid (BALF) were measured. The expression of proteins related with Dnmts, MeCP2, Romo1 in their lung tissues were assessed by immunohistochemical stain and fluorescent microscope. In addition, the level of ROS and DNA damage in the tissue were measured by ELISA. After ozone exposure on F0 generation, enhanced pause (Penh) values and the number of neutrophils in BALF were increased with concentration-dependent manner. Furthermore, Penh values and the number of neutrophils of their offspring (F1~F3) were continuously higher than those of offspring of air exposed mice. The expression of DNA methylation enzymes, Romo1 and 8-OHdG also increase in the ozone exposed mice than those in the air-exposed group. The ozone-exposed group showed higher levels of ROS and DNA damage than those in the air-exposed mice. Our observations suggest that the ozone exposure induces hyper-responsiveness and neutrophilic infiltration in airway through epigenetic change and DNA damage, which could be transmitted to the next generation.

The integrated effects of air pollution levels and meteorological conditions on asthma exacerbation: difference between moderate and severe exacerbation

배다정,신승우,장헌수,박종숙,김성렬,박춘식 대한결핵 및 호흡기학회 2017 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.124 No.-

Few studies have evaluated the integrated effects of meteorological conditions and air pollution levels on severity of exacerbations. Thus, we compared air pollutants levels between moderate and severe exacerbations. We recruited 143 asthmatics, who experienced at exacerbations between 2005 and 2013. A total of 618 exacerbations were evaluated in association with each component of air pollutants and meteorological conditions using a time-trend controlled case-crossover study design, and odds ratios were calculated for air pollutants on the day of exacerbation (T0) and up to 3 days before exacerbation (T-1 through T-3). In multi-pollutant models among total episode of exacerbations after controlling for other explanatory variables, a 1 ppm increase in O3 level most significantly augmented exacerbation: 155.7% (95% confidence interval [CI]: 1.34-4.86) for T-1 and 153.7% ([CI]: 1.32-4.86) for T-2 in winter (n=110) and 61.1%([CI]: 1.27-2.03) for T-1, 38.8%([CI]: 1.08-1.76) for T-2 and 39.7%([CI]: 1.11-1.75) for T-3 in summer (n=132). In the two stratified groups, severe exacerbations showed high associations with O3 levels on T-1 (214% increase/1ppm, [CI]: 1.31-7.51) in winter. As next factors in the total episodes of exacerbations, a 1 ppm increase in NO2 level augmented exacerbation: 98.1% ([CI]: 1.30-2.99) for T-1 and 95.8% ([CI]: 1.28-2.97) for T-2 in winter. This data indicates that O3 and NO2 exert a more apparent effect on severity in exacerbation of asthma. Data are obtained from SCH Biobank and funded by the South Korea's MoE as “the EHAP (2016001360002).”

P-43 Ozone exposure-mediated SLC26A4 gene expression was induced airway reactivity and inflammation in mice model

배다정,이현주,장헌수,박종숙,박춘식 대한결핵 및 호흡기학회 2016 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.121 No.-

SLC26A4 gene induces mucin genes and intraluminal acidification in the airways, SLC26A4 is supposed to be a key molecule in the ozone - induced AHR and neutrophilic inflammation. Thus, we evaluated the role of SLC26A4 gene in a chronic ozone exposure of murine model. 6weeks old BALB/C female mice were exposed to filtered air or O3 (2ppm for daily exposure 3hr time, 21days). Tetra-ammonium (TEA; 0, 0.1, 1, 10ng/kg) was administered into the ozone-exposed animals via intra- trachea route to block the effect of SLC26a4. Airway resistance was measured using Flexi vent and Bronchoalveolar lavage fluid (BALF) cells were differentially counted. SLC26A4 and Muc5ac proteins and genes were assessed by western blotting, immunohistochemistry and real-time PCR. The cytokines TNF-α, IFN-γ, IL-1beta, IL17 and Caspase-1 were analyzed by using a western blot analysis. The Materials were obtained from the SCHBC-bioback. SLC26A4 was significantly increased after ozone exposure in a time-dependent manner. Airway resistance and number of neutrophils in BALF fluids were increased significantly in the ozone exposed mice. SLC26A4 and Muc5ac RNA and protein levels of ozone exposed mice lungs were increased. These levels in TEA treated model were reduced compared to those in non-treated model. TEA significantly suppressed the ozone-induced increase of AHR and neutrophils(p-value<0.05). Also, western-blot analysis of inflammation cytokines was decreased the protein expression in TEA treated mice. SLC26A4 might be a target to alleviate ozone-induced AHR and neutrophilic inflammation.

천식과 후성유전학

배다정 ( Da Jeong Bae ),박춘식 ( Choon Sik Park ) 대한천식알레르기학회 2013 Allergy Asthma & Respiratory Disease Vol.1 No.1

For the past two decades, a huge number of genetic studies have been conducted to identify the genetic variants responsible for asthma risk. Several types of genetic and genomic approaches, including linkage analysis, candidate gene single nucleotide polymorphism studies, and whole genome-wide association studies have been applied. However, the genetic impacts of these studies are minimal because asthma is a complex syndrome affected by interaction with many environmental factors mediated by epigenetics. Epigenetics is alteration of genetic expression without changes of DNA sequence. Three major forms of epigenetic is DNA methylation, histone modfications and specific microRNA expression that are known to have vast effects on gene expression. However, knowledge regarding the epigenetic effect on the development of asthma and its traits is limited up to date. Recently, new data on epigenetics have been brought up to explain the phenotypic alterations of asthma. In this review, we present general concept of epigenetics, environmental factors inducting epigenetic changes and the background mechanisms in epigenetics behind development asthma and epigenetic therapy. (Allergy Asthma Respir Dis 1(1):4-10, 2013)Allergy Asthma Respir Dis 1(1):4-10, 2013)

청각장애 성인의 의사소통능력 향상을 위한 스크립트 기반 교재 개발

윤다정,배희원,김진,문수윤,송우진,김다영,이영미 한국언어치료학회 2016 한국언어치료학회 학술발표대회 논문집 Vol.2016 No.12

인공와우이식 청년의 의사소통 능력 향상을 위한 스크립트 기반의 청능훈련 도구 개발 및 효과에 대한 예비평가

윤다정(Da Jung Yun),배희원(Hui Won Bae),김 진(Jin Kim),이영미(Young-mee Lee) 한국청각언어재활학회 2018 Audiology and Speech Research Vol.14 No.4

Purpose: The purpose of the current study was to develop the script-based materials for auditory training and to investigate the effects of script-based auditory training for congenitally deaf young adults with cochlear implants (CIs). Methods: A total of eight scripts were developed based on the literature review and the survey for speech-language pathologists, adults with normal hearing (NH), and adults with CIs. For validation of the materials, words and sentences of auditory training tool were examined using the four-point Likert scale by 35 adults with NH, and words and sentences below 2 point were removed and replaced from the script. For evaluating the efficacy of the training, three adults with CIs attended the auditory training individually, two times per a week for 4 weeks. Their speech recognition skills and subjective communicative satisfaction were evaluated before and after auditory training, and analyzed using a one group pretest and post test design. Results: Although there were not significant increases in the speech recognition scores at the word and sentence level, there were significant increases in the overall communicative satisfaction on the results of the questionnaire. Conclusion: The current study suggests that auditory training using the script-based materials is useful in improving overall communicative satisfaction for young CI users who have limited communication skills.

F-94 : Free Paper Presentation ; Trans-Generational Transmission of Ozone - Induced Airway Dysfunction

박춘식,배다정,박종숙,장안수,박성우 대한결핵 및 호흡기학회 2013 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.116 No.-

Background: Epigenetics is responsible for the gene - environmental interaction of asthma development. Although Ozone is an important contributor to exacerbation of asthma, the role of epigenetics behind ozone - induced airway dysfunction is not known yet.We investigated trans-generational transmission of ozone - induced airway dysfunction and the underlying epigenetic changes in the lung of animal model. Method: 6 weeks old BALB/C female mice were exposed to filter air or O3 (2 ppm, 3 hr/day, day 1 to day 21). Airway resistance (Pehn), and BAL procedure were performed at weekly interval. mRNA expression of DNMT1, 3a, 3b, MeCP2, MBDs, HDAC3, Chrm1,2,3 and ADRß2 genes were measured in RNA extracted from lung tissue using Real-Time PCR. For trans-generational transmission study, 6weeks old BALB/C female mice (F0) were exposed to filter air (Air-F0) or O3 (1p pm, Ozone-F0) during pregnancy. Pehn was measured at 5 and 6 weeks of age in F1, F2 and F3 mice grown up in filter air, and cytokines (IL-1 alpha, beta, 4, 5, 8, 9, 10, 12, 13, 17, 22, 23) Lipoxin A4, Resolvin E1, Prostaglandin E2 were measured in BALF using ELISA kit. Result: After Ozone exposure, Pehn value was significantly increased in a time dependent manner with concomitant BAL neutrophilia. MBDs and HDAC3 increased at hour 3, while DNMT1, 3a, 3b, MeCP2 started to increase at day 14 and peaked at day 21 of Ozone exposure. In the trans-generational models, F1~ F3 mice born from Ozone-F0 showed persistent elevation of Pehn and BAL neutrophilia. IL-5, 8, 9,10, and 12 elevated in F1 of OzoneF0, but returned in F2 and F3 compared to those of Air F0. DNMT1,3a,3b of Ozone-F0 to Ozone-F3 increased, while Chrm2 and ADRß2 were decreased compared to those of AirF0. Conclusion: Ozone - induced airway dysfunction may be transmitted to F3 generation with altered expression of the genes related with airway function potentially via epigenetic changes.Background: Epigenetics is responsible for the gene - environmental interaction of asthma development. Although Ozone is an important contributor to exacerbation of asthma, the role of epigenetics behind ozone - induced airway dysfunction is not known yet.We investigated trans-generational transmission of ozone - induced airway dysfunction and the underlying epigenetic changes in the lung of animal model. Method: 6 weeks old BALB/C female mice were exposed to filter air or O3 (2 ppm, 3 hr/day, day 1 to day 21). Airway resistance (Pehn), and BAL procedure were performed at weekly interval. mRNA expression of DNMT1, 3a, 3b, MeCP2, MBDs, HDAC3, Chrm1,2,3 and ADRß2 genes were measured in RNA extracted from lung tissue using Real-Time PCR. For trans-generational transmission study, 6weeks old BALB/C female mice (F0) were exposed to filter air (Air-F0) or O3 (1p pm, Ozone-F0) during pregnancy. Pehn was measured at 5 and 6 weeks of age in F1, F2 and F3 mice grown up in filter air, and cytokines (IL-1 alpha, beta, 4, 5, 8, 9, 10, 12, 13, 17, 22, 23) Lipoxin A4, Resolvin E1, Prostaglandin E2 were measured in BALF using ELISA kit. Result: After Ozone exposure, Pehn value was significantly increased in a time dependent manner with concomitant BAL neutrophilia. MBDs and HDAC3 increased at hour 3, while DNMT1, 3a, 3b, MeCP2 started to increase at day 14 and peaked at day 21 of Ozone exposure. In the trans-generational models, F1~ F3 mice born from Ozone-F0 showed persistent elevation of Pehn and BAL neutrophilia. IL-5, 8, 9,10, and 12 elevated in F1 of OzoneF0, but returned in F2 and F3 compared to those of Air F0. DNMT1,3a,3b of Ozone-F0 to Ozone-F3 increased, while Chrm2 and ADRß2 were decreased compared to those of AirF0. Conclusion: Ozone - induced airway dysfunction may be transmitted to F3 generation with altered expression of the genes related with airway function potentially via epigenetic changes.

Prevalence of Respiratory Viral Infections in Korean Adult Asthmatics With Acute Exacerbations: Comparison With Those With Stable State

서기현,배다정,김지나,이호성,김용훈,박종숙,김명신,장헌수,손지혜,백동규,이준석,박춘식 대한천식알레르기학회 2017 Allergy, Asthma & Immunology Research Vol.9 No.6

Purpose: Viral infections are involved in ~50% of exacerbations among Caucasian adult asthmatics. However, there have been few reports on the causative virus of exacerbations in Korean adult asthmatics. Thus, we compared frequencies and types of viruses between lower respiratory tract illnesses (LRTIs) with exacerbations (exacerbated LRTIs) and those without exacerbations (stable LRTIs) to evaluate contribution of respiratory viruses to exacerbations. Methods: Viral RNA was extracted from sputum using the Viral Gene-spin™ Kit. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to detect adenovirus (ADV), metapneumovirus (MPV), parainfluenza virus (PIV) 1/2/3, influenza virus (IFV) A, IFV B, respiratory syncytial virus (RSV) A/B, and rhinovirus (RV) A. Results: Among the 259 patients, 210 underwent a single sputum examination, and the remaining 49 underwent 2 to 4 sputum examinations. Virus was detected in 68 of the 259 exacerbated episodes and in 11 of the 64 stable episodes. Among the exacerbated episodes, RV was the most frequently detected virus, followed by influenza A, parainfluenza, RSV A/B, and ADV. Among the 11 stable episodes, RV was most frequently detected. Detection rates of these viruses did not differ between the 2 groups (P>0.05). Thirty-five patients underwent the virus examination at 2 episodes of exacerbation, while 14 patients underwent at each time of exacerbated and stable episodes. Virus detection rate at the second examination was significantly higher in cases with 2 exacerbation episodes than in those with initial exacerbation and sequential stable episodes (P=0.003). A seasonal pattern was noted in the detection rates of RV (September to December), IFV (January to April), PIV (May to September), and RSV A/B (September to April). Conclusions: Respiratory viruses were identified in approximately 20% of LRTI irrespective of the presence of asthma exacerbation. RV and IFV A/B were most frequently detected. A group of patients experienced frequent viral infections followed by asthma exacerbations.

P-35 Elevation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis

이종욱,장헌수,이현주,정창안,배다정,송현지,박종숙,어수택,김용훈,서기현,박춘식 대한결핵 및 호흡기학회 2016 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.121 No.-

Background: Innate Th2 immune responses mediated by IL-33, TSLP, and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood. Methods: The BAL fluids were obtained from the biobank of Soonchunhyang University Bucheon Hospital. TSLP, IL-25, and IL-33 concentrations were measured in BAL fluids obtained from NCs (n=40) and from patients with IPF (n=100), NSIP (n=22), HP (n=20), and sarcoidosis (n=19). These concentrations were analyzed with respect to the development of IPF. Results: The TSLP and IL-33 levels were significantly higher in patients with IPF relative to the NCs (p=0.01 and p=0.0001, respectively), NSIP (p=4.95E-7 and p=0.0002, respectively), HP (p=0.00003 and p=0.000005, respectively), and sarcoidosis (p=0.003 and p= 0.0001, respectively). ROC curves of the TSLP and IL-33 levels revealed clear differences between the IPF and NCs [(AUC) = 0.655 and 0.706, respectively], as well as among the IPF and other ILDs (AUC=0.786 and 0.781, respectively). Cut-off values of 3.52pg/μg TSLP and 3.77pg/μg IL-33 were shown to differentiate between the IPF and NCs with 99.2% and 94.3% accuracy. Cut-off values of 4.66pg/μg TSLP and 2.52pg/μg IL-33 possessed 99.4% and 93.2% accuracy for differentiating among the IPF and other ILDs. Conclusions: Innate immune responses may be associated with the development of IPF. Furthermore, the IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic ILDs. Funding: NRF of Korea (2013R1A2A2A01068077)

의과대학부속병원 의사들의 양.한방 협진에 대한 인식

이은주,박한솔,이소영,배다정,이탁근,신현규,Lee, Eun-Joo,Park, Han-Sol,Lee, So-Young,Bae, Da-Jung,Lee, Tag-Gun,Shin, Hyeun-Kyoo 대한한방내과학회 2012 大韓韓方內科學會誌 Vol.33 No.3

Objectives : This study was aimed to promote the cooperative system of Korean and Western medicine in the dual health care system through a survey of physicians on recognition, problems and solution of the cooperative system. Methods : The research took place at Dongguk University Hospital from May 25 to 27, 2009 with 44 professors, residents, and interns employed by the hospital. Results : Of total 44 surveyed doctors, positive and moderate responses on the cooperative system between Korean and Western medicines were 40.9% and 43.2%, respectively. They scored it positive (62.5%) and moderate (31.3%) based on their experiences. These results can be supposed to represent the environment for the interdisciplinary medicine. Even in the interdisciplinary hospital of Korean and Western medicine, 68.2% of responders had no experience of the cooperative medical system. Expected interdisciplinary efficient departments were ordered rehabilitation medicine, neurology and orthopedics and associated with musculoskeletal disorders, the most frequent diseases treated by Korean traditional medicine. Conclusions : Korean and Western medical doctors, as medical personnel, intellectual persons as well as specialists, need a recognition and attitude to understand and respect each others' medicine. However, both groups also realize there are many complicated issues in the treatment of patients. It is difficult to require a change of Western doctors' perceptions and attitude toward Korean traditional medicine only with results of a survey. For the efficient cooperative system in the medical field, Korean medical doctors will need to study and consider specific problems mentioned by Western medicine.