1.Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles
Jinho YANG ; Goohyeon HONG ; Youn-Seup KIM ; Hochan SEO ; Sungwon KIM ; Andrea MCDOWELL ; Won Hee LEE ; You-Sun KIM ; Yeon-Mok OH ; You-Sook CHO ; Young Woo CHOI ; You-Young KIM ; Young-Koo JEE ; Yoon-Keun KIM
Allergy, Asthma & Immunology Research 2020;12(4):669-683
Purpose:
Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease.
Methods:
We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis.
Results:
Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81.
Conclusions
The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.
2.Lung Disease Diagnostic Model Through IgG Sensitization to Microbial Extracellular Vesicles
Jinho YANG ; Goohyeon HONG ; Youn-Seup KIM ; Hochan SEO ; Sungwon KIM ; Andrea MCDOWELL ; Won Hee LEE ; You-Sun KIM ; Yeon-Mok OH ; You-Sook CHO ; Young Woo CHOI ; You-Young KIM ; Young-Koo JEE ; Yoon-Keun KIM
Allergy, Asthma & Immunology Research 2020;12(4):669-683
Purpose:
Recently, there has been a rise in the interest to understand the composition of indoor dust due to its association with lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and lung cancer. Furthermore, it has been found that bacterial extracellular vesicles (EVs) within indoor dust particles can induce pulmonary inflammation, suggesting that these might play a role in lung disease.
Methods:
We performed microbiome analysis of indoor dust EVs isolated from mattresses in apartments and hospitals. We developed diagnostic models based on the bacterial EVs antibodies detected in serum samples via enzyme-linked immunosorbent assay (ELISA) in this analysis.
Results:
Proteobacteria was the most abundant bacterial EV taxa observed at the phylum level while Pseudomonas, Enterobacteriaceae (f) and Acinetobacter were the most prominent organisms at the genus level, followed by Staphylococcus. Based on the microbiome analysis, serum anti-bacterial EV immunoglobulin G (IgG), IgG1 and IgG4 were analyzed using ELISA with EV antibodies that targeted Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae and Pseudomonas aeruginosa. The levels of anti-bacterial EV antibodies were found to be significantly higher in patients with asthma, COPD and lung cancer compared to the healthy control group. We then developed a diagnostic model through logistic regression of antibodies that showed significant differences between groups with smoking history as a covariate. Four different variable selection methods were compared to construct an optimal diagnostic model with area under the curves ranging from 0.72 to 0.81.
Conclusions
The results of this study suggest that ELISA-based analysis of anti-bacterial EV antibodies titers can be used as a diagnostic tool for lung disease. The present findings provide insights into the pathogenesis of lung disease as well as a foundation for developing a novel diagnostic methodology that synergizes microbial EV metagenomics and immune assays.
4.IgG Sensitization to Extracellular Vesicles in Indoor Dust Is Closely Associated With the Prevalence of Non-Eosinophilic Asthma, COPD, and Lung Cancer.
You Sun KIM ; Jun Pyo CHOI ; Min Hye KIM ; Han Ki PARK ; Sejung YANG ; Youn Seup KIM ; Tae Bum KIM ; You Sook CHO ; Yeon Mok OH ; Young Koo JEE ; Sang Do LEE ; Yoon Keun KIM
Allergy, Asthma & Immunology Research 2016;8(3):198-205
PURPOSE: Recent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation, which is a characteristic pathology in patients with severe asthma and chronic obstructive pulmonary disease (COPD). In addition, COPD is known to be an important risk factor for lung cancer, irrespective of cigarette smoking. Here, we evaluated whether sensitization to indoor dust EVs is a risk for the development of asthma, COPD, or lung cancer. METHODS: Serum IgG antibodies against dust EVs were measured in 90 healthy control subjects, 294 asthmatics, 242 COPD patients, and 325 lung cancer patients. Serum anti-dust EV IgG titers were considered high if they exceeded a 95 percentile value of the control subjects. Age-, gender-, and cigarette smoke-adjusted multiple logistic regression analyses were performed to determine odds ratios (ORs) for asthma, COPD, and lung cancer patients vs the control subjects. RESULTS: In total, 4.4%, 13.6%, 29.3%, and 54.9% of the control, asthma, COPD, and lung cancer groups, respectively, had high serum anti-dust EV IgG titers. Adjusted multiple logistic regression revealed that sensitization to dust EVs (high serum anti-dust EV IgG titer) was an independent risk factor for asthma (adjusted OR, 3.3; 95% confidence interval [CI], 1.1-10.0), COPD (adjusted OR, 8.0; 95% CI, 2.0-32.5) and lung cancer (adjusted OR, 38.7; 95% CI, 10.4-144.3). CONCLUSIONS: IgG sensitization to indoor dust EVs appears to be a major risk for the development of asthma, COPD, and lung cancer.
Antibodies
;
Asthma*
;
Dust*
;
Humans
;
Immunoglobulin G*
;
Logistic Models
;
Lung Neoplasms*
;
Lung*
;
Odds Ratio
;
Pathology
;
Pneumonia
;
Prevalence*
;
Pulmonary Disease, Chronic Obstructive*
;
Risk Factors
;
Smoking
;
Tobacco Products
5.Methazolamide-induced toxic epidermal necrolysis confirmed by lymphocyte activation test.
Kyu Hyung HAN ; Ku Hyun HONG ; Doh Hyung KIM ; Youn Seup KIM ; Jae Suk PARK ; Seung Heon KIM ; Young Koo JEE
Allergy, Asthma & Respiratory Disease 2016;4(4):301-304
Among various dermatological entities, toxic epidermal necrolysis (TEN) is a rare but potentially fatal delayed hypersensitivity reaction to numerous medications. A 38-year-old male presented with systemic hypersensitivity reaction, such as high fever, pain in the eyes, and diffuse pruritic erythematous maculopapular eruptions with multiple targetoid plaques that became vesicular and bullous. Oral mucosa and conjunctivae were involved. The first sign appeared about 1 week after taking methazolamide (50 mg twice a day) for the management of glaucomatous eyes. Although methazolamide was discontinued, blistering and skin denudation progressed to affect up to 80% of the body surface area and a positive Nikolsky sign was noted. High fever also persisted. Skin lesions started to improve after 2 weeks of management and fever subsided. Cutaneous lesions improved with minimal permanent sequele 2 months later. HLA-B*5901 was found by high-resolution genotyping. The lymphocyte activation test performed 6 months after remission showed a positive response to methazolamide challenge. This is the first case of methazolamide-induced TEN in which methazolamide was confirmed as a culprit drug by the lymphocyte activation test.
Adult
;
Blister
;
Body Surface Area
;
Conjunctiva
;
Fever
;
Humans
;
Hypersensitivity
;
Hypersensitivity, Delayed
;
Lymphocyte Activation*
;
Lymphocytes*
;
Male
;
Methazolamide
;
Mouth Mucosa
;
Skin
;
Stevens-Johnson Syndrome*
6.A Case of Advanced Malignant Pleural Mesothelioma Treatment with Chemotherapy and Photodynamic Therapy.
Tuberculosis and Respiratory Diseases 2015;78(1):36-40
Malignant pleural mesothelioma (MPM) is an aggressive, treatment-resistant, and generally fatal disease. A 68-year-old male who was diagnosed with MPM at another hospital came to our hospital with dyspnea. We advised him to take combination chemotherapy but he refused to take the treatment. That was because he had already received chemotherapy with supportive care at another hospital but his condition worsened. Thus, we recommended photodynamic therapy (PDT) to deal with the dyspnea and MPM. After PDT, the dyspnea improved and the patient then decided to take the combination chemotherapy. Our patient received chemotherapy using pemetrexed/cisplatin. Afterwards, he received a single PDT treatment and then later took chemotherapy using gemcitabine/cisplatin. The patient showed a survival time of 27 months, which is longer than median survival time in advanced MPM patients. Further research and clinical trials are needed to demonstrate any synergistic effect between the combination chemotherapy and PDT.
Aged
;
Drug Therapy*
;
Drug Therapy, Combination
;
Dyspnea
;
Humans
;
Male
;
Mesothelioma*
;
Photochemotherapy*
;
Pleura
7.Experience with Elizabethkingia meningoseptica Infection in Adult Patients at a Tertiary Hospital.
Hyun Don JOO ; Sun Young ANN ; Sung Hyeok RYOU ; Youn Seup KIM ; Jong Wan KIM ; Doh Hyung KIM
Korean Journal of Critical Care Medicine 2015;30(4):241-248
BACKGROUND: Few reports have documented the clinical characteristics and treatment outcomes of adult patients with Elizabethkingia meningoseptica infection. METHODS: Medical records of patients over 18 years of age and suspected of having an E. meningoseptica infection from March 1, 2006 to February 28, 2013 were reviewed retrospectively. Their clinical characteristics, antimicrobial susceptibility results, and treatment outcomes were analyzed. RESULTS: E. meningoseptica was isolated from 30 patients. Median age was 68.5 years, and infections were more frequent in males (17, 56.7%). The most common isolation source was sputum (23, 76.7%), and pneumonia was the most common condition (21, 70%) after excluding two cases of colonization. This bacterium was most susceptible to minocycline (27, 90%) and fluoroquinolones, including levofloxacin (20, 66.7%) and ciprofloxacin (18, 60%). The mortality rate due directly to E. meningoseptica infection was 20% (6/30), and uncontrolled pneumonia was the only cause of death. After isolating E. meningoseptica, the numbers of patients with pneumonia (9/9, 100% vs. 12/21, 57.1%), history of hemodialysis (5/9, 55.6% vs. 3/21, 14.3%), tracheostomy (8/9, 88.9 vs. 10/21, 47.6%), and median Charlson comorbidity index score (6 [range, 3-9] vs. 4 [range, 0-9]) were significantly higher in non-survivors than those in survivors (p < 0.05, for each). However, only 12 (40%) patients received appropriate antibiotics. CONCLUSIONS: E. meningoseptica infection most commonly presented as pneumonia in adults with severe underlying diseases. Despite the high mortality rate, the rate of appropriate antibiotic use was notably low.
Adult*
;
Anti-Bacterial Agents
;
Cause of Death
;
Chryseobacterium
;
Ciprofloxacin
;
Colon
;
Comorbidity
;
Cross Infection
;
Fluoroquinolones
;
Humans
;
Levofloxacin
;
Male
;
Medical Records
;
Minocycline
;
Mortality
;
Pneumonia
;
Renal Dialysis
;
Retrospective Studies
;
Sputum
;
Survivors
;
Tertiary Care Centers*
;
Tracheostomy
8.Experience with Elizabethkingia meningoseptica Infection in Adult Patients at a Tertiary Hospital
Hyun Don JOO ; Sun Young ANN ; Sung Hyeok RYOU ; Youn Seup KIM ; Jong Wan KIM ; Doh Hyung KIM
The Korean Journal of Critical Care Medicine 2015;30(4):241-248
BACKGROUND: Few reports have documented the clinical characteristics and treatment outcomes of adult patients with Elizabethkingia meningoseptica infection. METHODS: Medical records of patients over 18 years of age and suspected of having an E. meningoseptica infection from March 1, 2006 to February 28, 2013 were reviewed retrospectively. Their clinical characteristics, antimicrobial susceptibility results, and treatment outcomes were analyzed. RESULTS: E. meningoseptica was isolated from 30 patients. Median age was 68.5 years, and infections were more frequent in males (17, 56.7%). The most common isolation source was sputum (23, 76.7%), and pneumonia was the most common condition (21, 70%) after excluding two cases of colonization. This bacterium was most susceptible to minocycline (27, 90%) and fluoroquinolones, including levofloxacin (20, 66.7%) and ciprofloxacin (18, 60%). The mortality rate due directly to E. meningoseptica infection was 20% (6/30), and uncontrolled pneumonia was the only cause of death. After isolating E. meningoseptica, the numbers of patients with pneumonia (9/9, 100% vs. 12/21, 57.1%), history of hemodialysis (5/9, 55.6% vs. 3/21, 14.3%), tracheostomy (8/9, 88.9 vs. 10/21, 47.6%), and median Charlson comorbidity index score (6 [range, 3-9] vs. 4 [range, 0-9]) were significantly higher in non-survivors than those in survivors (p < 0.05, for each). However, only 12 (40%) patients received appropriate antibiotics. CONCLUSIONS: E. meningoseptica infection most commonly presented as pneumonia in adults with severe underlying diseases. Despite the high mortality rate, the rate of appropriate antibiotic use was notably low.
Adult
;
Anti-Bacterial Agents
;
Cause of Death
;
Chryseobacterium
;
Ciprofloxacin
;
Colon
;
Comorbidity
;
Cross Infection
;
Fluoroquinolones
;
Humans
;
Levofloxacin
;
Male
;
Medical Records
;
Minocycline
;
Mortality
;
Pneumonia
;
Renal Dialysis
;
Retrospective Studies
;
Sputum
;
Survivors
;
Tertiary Care Centers
;
Tracheostomy
9.A Case of Bronchial Artery Aneurysm in Cavitary Pulmonary Tuberculosis.
Woo Hee CHO ; Hyeok Chan KWON ; Yong Ho JANG ; Suk Bin JANG ; Do Hyung KIM ; Youn Seup KIM ; Jae Seuk PARK
Korean Journal of Medicine 2014;86(2):228-231
A bronchial artery (BA) aneurysm is a rare, life-threatening disease when it ruptures. Recently, we experienced a case of massive hemoptysis due to a BA aneurysm rupture in a pulmonary tuberculosis cavity, treated with BA embolization followed by surgical resection of the cavitary lesion. To our knowledge, this is the first case of a BA aneurysm associated with cavitary pulmonary tuberculosis.
Aneurysm*
;
Bronchial Arteries*
;
Hemoptysis
;
Rupture
;
Tuberculosis
;
Tuberculosis, Pulmonary*
10.A Case of Bronchial Artery Aneurysm in Cavitary Pulmonary Tuberculosis.
Woo Hee CHO ; Hyeok Chan KWON ; Yong Ho JANG ; Suk Bin JANG ; Do Hyung KIM ; Youn Seup KIM ; Jae Seuk PARK
Korean Journal of Medicine 2014;86(2):228-231
A bronchial artery (BA) aneurysm is a rare, life-threatening disease when it ruptures. Recently, we experienced a case of massive hemoptysis due to a BA aneurysm rupture in a pulmonary tuberculosis cavity, treated with BA embolization followed by surgical resection of the cavitary lesion. To our knowledge, this is the first case of a BA aneurysm associated with cavitary pulmonary tuberculosis.
Aneurysm*
;
Bronchial Arteries*
;
Hemoptysis
;
Rupture
;
Tuberculosis
;
Tuberculosis, Pulmonary*

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