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2.  Bilateral Segmental Neurofibromatosis on the Face 
Annals of Dermatology  2015;27(1):115-117.
doi:10.5021/ad.2015.27.1.115
PMCID: PMC4323594
3.  Disease Awareness and Management Behavior of Patients with Atopic Dermatitis: A Questionnaire Survey of 313 Patients 
Annals of Dermatology  2015;27(1):40-47.
Background
Patients with atopic dermatitis (AD) should be relatively well informed about the disorder to control their condition and prevent flare-ups. Thus far, there is no accurate information about the disease awareness levels and therapeutic behavior of AD patients.
Objective
To collect data on patients' knowledge about AD and their behavior in relation to seeking information about the disease and its treatment.
Methods
We performed a questionnaire survey on the disease awareness and self-management behavior of AD patients. A total of 313 patients and parents of patients with AD who had visited the The Catholic University of Korea, Catholic Medical Center between November 2011 and October 2012 were recruited. We compared the percentage of correct answers from all collected questionnaires according to the demographic and disease characteristics of the patients.
Results
Although dermatologists were the most frequent disease information sources and treatment providers for the AD patients, a significant proportion of participants obtained information from the Internet, which carries a huge amount of false medical information. A considerable number of participants perceived false online information as genuine, especially concerning complementary and alternative medicine treatments of AD, and the adverse effects of steroids. Some questions on AD knowledge had significantly different answers according to sex, marriage status, educational level, type of residence and living area, disease duration, disease severity, and treatment history with dermatologists.
Conclusion
Dermatologists should pay more attention to correcting the common misunderstandings about AD to reduce unnecessary social/economic losses and improve treatment compliance.
doi:10.5021/ad.2015.27.1.40
PMCID: PMC4323601
Awareness; Complementary therapies; Dermatitis; atopic; Disease management; Information seeking behavior
4.  Clinical Application of Exhaled Nitric Oxide Measurements in a Korean Population 
Nitric oxide (NO) is a biologic mediator of various physiologic functions. Recent evidence suggests the clinical utility of fractional exhaled NO (FeNO) as a biomarker for assessing asthma and other respiratory diseases. FeNO methodologies have been recently standardized by international research groups and subsequently validated in several Korean population studies. Normal ranges for FeNO have been reported for various ethnic groups, and the clinical utility has been widely evaluated in asthma and various respiratory diseases. Based on current evidence including most of Korean population data, this position paper aims to introduce the methodological considerations, and provide the guidance for the proper clinical application of FeNO measurements in Korean populations.
doi:10.4168/aair.2015.7.1.3
PMCID: PMC4274466  PMID: 25553257
Exhaled nitric oxide; reference value; guideline; position paper; asthma
5.  Airway Smooth Muscle Sensitivity to Methacholine in Precision-Cut Lung Slices (PCLS) from Ovalbumin-induced Asthmatic Mice 
Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (ΔAW) was observed. In contrast to the AHR in vivo, the EC50 of MCh for ΔAW from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced ΔAW by 60 mM K+ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced ΔAW of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.
doi:10.4196/kjpp.2015.19.1.65
PMCID: PMC4297764  PMID: 25605999
Airway; Asthma; Lung slice; Smooth muscle
6.  Effects of Age on Arterial Stiffness and Blood Pressure Variables in Patients with Newly Diagnosed Untreated Hypertension 
Korean Circulation Journal  2015;45(1):44-50.
Background and Objectives
To investigate the impact of age on arterial stiffness and blood pressure (BP) variables in newly diagnosed untreated hypertension (HT).
Subjects and Methods
A total of 144 patients with newly diagnosed untreated HT were divided into two groups: young group (age ≤50 years, n=71), and old group (age >50 years, n=73). BP variables were measured on office or 24 hours ambulatory BP monitoring (ABPM). Parameters of arterial stiffness were measured on pulse wave velocity (PWV). Pulse wave analysis (PWA) was compared.
Results
Although office BP and pulse pressure (PP) were significantly (p<0.05) higher in the young group than in the old group, BP and PP on ABPM were not significantly different. Central systolic BP and PP, augmentation pressure, augmentation index on PWA, and PWV were significantly higher or faster in the old group compared to that in the young group. Age showed significant positive correlation with both PWV and PWA variables in the young group with HT. However, age only showed significant positive correlation with PWV in the old group with HT. In the young group with HT, PWA variable showed better correlation with age than PWV.
Conclusion
Considering BP levels on ABPM, office BP is prone to be overestimated in young patients with HT. Parameters of arterial stiffness measured by PWV and PWA were more affected by age rather than by BP level in patients with HT. Therefore, PWA variable might be a more sensitive marker of arterial stiffness in young patients with HT. However, PWV might be a better marker for old patients with HT.
doi:10.4070/kcj.2015.45.1.44
PMCID: PMC4310979  PMID: 25653703
Hypertension; Vascular stiffness; Aging
7.  Validation of the Korean version of the European Community Respiratory Health Survey screening questionnaire for use in epidemiologic studies for adult asthma 
Asia Pacific Allergy  2015;5(1):25-31.
Background
Standardized questionnaire is one of key instruments for general population surveys.
Objective
The present study aimed to develop and validate the Korean version of the European Community Respiratory Health Survey (ECRHS) screening questionnaire for adult asthma surveys.
Methods
The ECRHS screening questionnaire was translated into Korean language according to the international criteria. Study participants were prospectively recruited from six referral hospitals and one health check-up center. Comprehensibility of the translation was tested in a pilot study of 10 patients. The reliability was evaluated by internal consistency and test-retest repeatability. Validity was assess with regard to physician-diagnosed asthma.
Results
A total of 100 adult asthma patients and 134 volunteers were recruited. Reliability was examined for 10 items in 100 asthmatics; Cronbach α coefficients were 0.84, and test-retest repeatability was good (Cohen κ coefficient, 0.71-1.00). Validity was assessed for 8 items in 234 participants; in particular, 'recent wheeze' showed a high sensitivity (0.89) for physician-diagnosed asthma. 'Recent asthma attack' and 'current asthma medication' showed high specificity (0.96-0.98).
Conclusion
The present study demonstrated that the Korean version of the ECRHS screening questionnaire was comprehensible, reliable and valid. We suggest the questionnaire to be utilized in further epidemiological studies for asthma in Korean adult populations.
doi:10.5415/apallergy.2015.5.1.25
PMCID: PMC4313752  PMID: 25653917
Asthma; Epidemiology; Questionnaires
8.  Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk 
Nature genetics  2014;46(6):533-542.
Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted the largest genome-wide association study in East Asians with 14,963 CRC cases and 31,945 controls and identified six new loci associated with CRC risk (P = 3.42 × 10−8 to 9.22 × 10−21) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcription regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9) and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC loci. Our study provides insights into the genetic basis of CRC and suggests new biological pathways.
doi:10.1038/ng.2985
PMCID: PMC4068797  PMID: 24836286
9.  Foreign Body Reaction due to a Retained Cuff from a Central Venous Catheter 
Annals of Dermatology  2014;26(6):781-783.
doi:10.5021/ad.2014.26.6.781
PMCID: PMC4252689  PMID: 25473244
10.  Role of Peritoneal Lavage Cytology and Prediction of Prognosis and Peritoneal Recurrence After Curative Surgery for Colorectal Cancer 
Annals of Coloproctology  2014;30(6):266-273.
Purpose
In colorectal cancer, the role of detecting free malignant cells from peritoneal lavage is currently unclear. In this study, we investigated the positive rate of free malignant cells in peritoneal lavage fluid and their predictive value for prognosis and peritoneal recurrence after a curative resection.
Methods
From October 2009 to December 2011, in a prospective manner, we performed cytologic examinations of peritoneal lavage fluid obtained just after the abdominal incision from 145 patients who underwent curative surgery for colorectal cancer. We used proportional hazard regression models to analyze the predictive role of positive cytology for peritoneal recurrence and survival.
Results
Among total 145 patients, six patients (4.1%) showed positive cytology. During the median follow-up of 32 months (range, 8-49 months), 27 patients (18.6%) developed recurrence. Among them, 5 patients (3.4%) showed peritoneal carcinomatosis. In the multivariate analysis, positive cytology was an independent predictive factor for peritoneal recurrence (hazard ratio [HR], 136.5; 95% confidence interval [CI], 12.2-1,531.9; P < 0.0001) and an independent poor prognostic factor for overall survival (HR, 11.4; 95% CI, 1.8-72.0; P = 0.009) and for disease-free survival (HR, 11.1; 95% CI, 3.4-35.8; P < 0.0001).
Conclusion
Positive cytology of peritoneal fluid was significantly associated with peritoneal recurrence and worse survival in patients undergoing curative surgery for colorectal cancer. Peritoneal cytology might be a useful tool for selecting patients who need intraperitoneal or systemic chemotherapy.
doi:10.3393/ac.2014.30.6.266
PMCID: PMC4286773  PMID: 25580413
Peritoneal metastasis; Cytology; Colorectal neoplasms; Survival; Prognosis
11.  Risk Factors for Asthma-Related Healthcare Use: Longitudinal Analysis Using the NHI Claims Database in a Korean Asthma Cohort 
PLoS ONE  2014;9(11):e112844.
Background
Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data.
Methods and Results
Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability.
Conclusion
We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.
doi:10.1371/journal.pone.0112844
PMCID: PMC4232512  PMID: 25397972
12.  Different protein expression associated with chemotherapy response in oropharyngeal cancer according to HPV status 
BMC Cancer  2014;14(1):824.
Backgound
Oropharyngeal cancer (OPC) associated with human papilloma virus (HPV OPC) shows better treatment outcomes than non-HPV OPC. We investigated the expression of p53, β-tubulin, bcl-2 and ERCC 1, which are well-known biomarkers to predict the chemotherapy response, according to HPV status in OPC patients.
Methods
Patients who treated with at least 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced oropharyngeal cancer were reviewed. HPV PCR and immunohistochemical stain was done in paraffin embedded tumor tissue and evaluated the relation with the chemotherapy response and survival outcomes according to HPV status.
Results
Seventy-four patients were enrolled for this study and all patients received induction chemotherapy with docetaxel, 5-FU and cisplatin. After induction chemotherapy, complete response (CR) was shown in 22 patients (30%) and partial response (PR) in 46 patients (62%). HPV + was detected in 21 patients (28%), while 35 patients (47%) showed p16+ expression by IHC analysis. p16 positive patients showed better overall response, PFS and OS than p16 negative patients. p53 and class III beta-tubulin expression were significantly higher in HPV- and p16- than HPV + and p16+ patients. Conversely, bcl-2 expression was greater in HPV + or p16+ than HPV- or p16- patients. ERCC1 expression did not differ significantly according to HPV status. In multivariate analyses, early T stage (p = 0.036) and good PS (PS 0) (p = 0.029) showed a better 3Y-PFS rate, and low p53 expression (p = 0.012) and complete response after induction chemotherapy (p = 0.026) were highly associated with 3Y-OS rate. Low expression of p53 and p16 positive patients showed significantly prolonged OS than others (p = 0.010).
Conclusion
P53, class III beta-tubulin and bcl-2 were differently expressed in OPC according to HPV status and present study suggested the underlying mechanism of better response to chemotherapy in case of HPV OPC than non-HPV OPC. Among these biomarkers, p53 is the strongest prognostic marker in OPC and p53 in addition to p16 support the rationale to study of de-escalation strategy for OPC.
doi:10.1186/1471-2407-14-824
PMCID: PMC4232654  PMID: 25380690
Oropharyngeal cancer; HPV; p16; Chemotherapy; p53; Beta tubulin; bcl-2
13.  Reference Ranges and Determinant Factors for Exhaled Nitric Oxide in a Healthy Korean Elderly Population 
Purpose
Exhaled nitric oxide (NO) is a useful non-invasive biomarker for asthma diagnosis; however, the literature suggests that exhaled NO levels may be affected by demographic factors. The present analysis investigated determinant factors that present exhaled NO reference levels for Korean elderly adults.
Methods
For reference levels, we analyzed the baseline data of healthy adult participants in the Ansung cohort. The fraction of exhaled NO (FeNO) was measured by NIOX MINO®. The characterization of the subjects was performed through structured questionnaires, spirometry, and methacholine challenge tests. To validate the diagnostic utility of the determined reference levels, asthma patients were recruited from medical institutions for FeNO measurement.
Results
A total of 570 healthy subjects were analyzed (mean age, 59.9±12.3; male, 37.0%) for reference levels. FeNO levels significantly correlated with weight, height, body mass index, atopy, or forced expiratory volume in 1 second % predicted by simple linear regression analysis. Multiple linear regression analysis identified gender as an independent determinant for FeNO levels; subsequently, the reference values for FeNO were 18.2±10.6 ppb (5th to 95th percentile, 6.0 to 37.4 ppb) for males and 12.1±6.9 ppb (5th to 95th percentile, 2.5 to 27.0 ppb) for females. The diagnostic utility of FeNO reference levels was validated by receiver operating curve analysis (area under curve, 0.900 for males and 0.885 for females) for diagnosing asthma. The optimal cutoff values for the prediction of asthma were 30.5 ppb for males and 20.5 ppb for females.
Conclusions
The current analysis presented reference ranges and the diagnostic utility of FeNO levels for asthma in Korean elderly adults.
doi:10.4168/aair.2014.6.6.504
PMCID: PMC4214970  PMID: 25374749
Adult; asthma; nitric oxide; reference values
14.  A Ganglion Cyst of the Temporomandibular Joint 
Archives of Plastic Surgery  2014;41(6):777-780.
doi:10.5999/aps.2014.41.6.777
PMCID: PMC4228227  PMID: 25396197
15.  Chlorinated Coumarins from the Polypore Mushroom, Fomitopsis officinalis, and their Activity Against Mycobacterium tuberculosis 
Journal of natural products  2013;76(10):10.1021/np400497f.
An EtOH extract of the polypore mushroom, Fomitopsis officinalis afforded two new naturally occurring chlorinated coumarins which were identified as the previously synthesized compounds, 6-chloro-4-phenyl-2H-chromen-2-one (1) and ethyl 6-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (2). The structures of the two isolates were deduced ab initio by spectroscopic methods and confirmed by chemical synthesis. In addition, an analogue of each was synthesized as of 7-chloro-4-phenyl-2H-chromen-2-one (3) and ethyl 7-chloro-2-oxo-4-phenyl-2H-chromen-3-carboxylate (4). All four compounds were characterized physicochemically, and their antimicrobial activity profiles revealed a narrow spectrum of activity with lowest MICs against the Mycobacterium tuberculosis complex.
doi:10.1021/np400497f
PMCID: PMC3851412  PMID: 24087924
16.  Importance of Reciprocal Balance of T Cell Immunity in Mycobacterium abscessus Complex Lung Disease 
PLoS ONE  2014;9(10):e109941.
Background
Little is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC) infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lung disease patients with antibiotics can reflect the disease-associated characteristics.
Methods
A total of 22 immunomolecules in 24 MABC lung disease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system.
Results
In general, the pre-treatment levels of T helper type 1 (Th1)-related cytokines, i.e., interferon (IFN)-γ and interleukin (IL)-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-γ-induced protein (IP)-10 and monokine induced by IFN-γprotein (MIG) were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion.
Conclusion
Reduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lung disease, and the immunomolecules IP-10 and MIG, induced through IFN-γ, may serve as key markers for indicating the treatment outcome.
doi:10.1371/journal.pone.0109941
PMCID: PMC4190320  PMID: 25295870
17.  Multiple-dose pharmacokinetics and pharmacodynamics of evogliptin (DA-1229), a novel dipeptidyl peptidase IV inhibitor, in healthy volunteers 
Purpose
Evogliptin (DA-1229) is a novel, potent, and selective dipeptidyl peptidase IV (DPP-IV) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study aimed to investigate the pharmacokinetic and pharmacodynamic profiles and tolerability of evogliptin after repeated oral administration in healthy subjects.
Patients and methods
A block-randomized, double-blind, placebo-controlled, multiple-dose, dose-escalation study was performed in a total of 30 subjects. Repeated once-daily doses of 5, 10, or 20 mg evogliptin or the same doses of placebo were orally administered to ten subjects in each dosage group for 10 days. Subjects in each group were randomized to receive evogliptin or placebo with a ratio of 8:2. Pharmacokinetics of evogliptin were evaluated, with its concentrations in serial plasma and urine samples collected following the first and last administrations. DPP-IV activity and glucagon-like peptide-1, glucose, and insulin levels were quantified to evaluate evogliptin’s pharmacodynamics on the first and last dosing days.
Results
All participants completed the study without any serious or severe adverse event. The evogliptin plasma concentration reached its peak within 4–5 hours and decreased relatively slowly, with a terminal elimination half-life of 33–39 hours. Repeated administration resulted in a 1.4- to 1.5-fold accumulation. Evogliptin’s systemic exposure and inhibition of plasma DPP-IV activity increased in a dose-dependent manner. Inhibition of DPP-IV activity >80% was sustained over 24 hours in all evogliptin dose groups and provided an increase in postprandial active glucagon-like peptide-1 levels by 1.5- to 2.4-fold. Postprandial glucose levels in the evogliptin-treated groups were reduced 20%–35% compared to placebo, but were not accompanied by increased insulin levels.
Conclusion
Repeated administration of evogliptin in healthy subjects was well tolerated and exhibited linear pharmacokinetics within the 5–20 mg dose range. A once-daily regimen of 5–20 mg evogliptin effectively inhibited DPP-IV activity.
doi:10.2147/DDDT.S65678
PMCID: PMC4199987  PMID: 25336915
DPP-IV; GLP-1; insulin; glucagon-like peptide-1; glucose
18.  The impact of sinusitis on the long-term clinical outcomes of asthma 
Asia Pacific Allergy  2014;4(4):222-229.
Background
Upper respiratory diseases have been linked with lower respiratory diseases. However, the long-term effect of sinusitis on the clinical outcomes of asthma has not been fully evaluated.
Objective
The aim of this study was to investigate the impact of sinusitis on the disease progression of asthma.
Methods
Seventy-five asthmatic patients confirmed with the methacholine bronchial provocation test or bronchodilator response were included. The study patients underwent paranasal sinus x-ray upon their asthma evaluation and they visited the hospital at least 3 years or longer. We retrospectively reviewed their medical records and compared data according to the presence of comorbid sinusitis.
Results
Among the 75 asthmatic subjects, 38 subjects (50.7%) had radiologic evidence of sinusitis. Asthmatics with sinusitis had significantly lower forced expiratory volume in 1 second (FEV1; 79.2% vs. 88.2%) and PC20 values (5.2 mg/mL vs. 8.9 mg/mL) compared to asthmatics without sinusitis at the time of diagnosis. This difference in FEV1 disappeared (82.6% vs. 87.2%) in the 3-year follow-up, although FEV1 was more variable (31.7% vs. 23.5%) and worst FEV1 was also significantly lower in patients with sinusitis compared to those without (70.9% vs. 79.0%). There were no significant differences in the number of hospital visits, acute exacerbations, and scores for the asthma control test.
Conclusion
Although sinusitis was associated with lower baseline lung function and higher hyperreactivity, sinusitis was not related with significant deterioration in lung function over 3 years of follow-up. Asthmatics with sinusitis showed more variability in lung function during the follow-up period. Healthcare utilization was not different except antibiotics use.
doi:10.5415/apallergy.2014.4.4.222
PMCID: PMC4215430  PMID: 25379482
Sinusitis; Asthma; Disease progression; Forced expiratory volume
19.  Lamotrigine-induced toxic epidermal necrolysis confirmed by in vitro granulysin and cytokine assays 
Asia Pacific Allergy  2014;4(4):253-256.
Lamotrigine is a recent medication which is prescribed for various neuropsychiatric conditions. It is generally well-tolerated, but recent pharmacoepidemiological evidence suggests that lamotrigine is associated with risks of developing severe cutaneous drug reactions like toxic epidermal necrolysis (TEN). However, there still remains the diagnostic challenge regarding how to confirm the drug causality in suspected cases. In most cases so far, lamotrigine causality has not been objectively demonstrated, which was possibly due to high risk of oral challenge tests or the lack of useful in vitro drug assays. Here we report a case of lamotrigine-induced TEN, of which the drug causality was confirmed by in vitro granulysin and cytokine assays.
doi:10.5415/apallergy.2014.4.4.253
PMCID: PMC4215432  PMID: 25379485
Toxic epidermal necrolysis; Lamotrigine; Granulysin; Natural killer cells; Cyclosporine
20.  Chronic Low Dose Chlorine Exposure Aggravates Allergic Inflammation and Airway Hyperresponsiveness and Activates Inflammasome Pathway 
PLoS ONE  2014;9(9):e106861.
Background
Epidemiologic clinical studies suggested that chronic exposure to chlorine products is associated with development of asthma and aggravation of asthmatic symptoms. However, its underlying mechanism was not clearly understood. Studies were undertaken to define the effects and mechanisms of chronic low-dose chlorine exposure in the pathogenesis of airway inflammation and airway hyperresponsiveness (AHR).
Methods
Six week-old female BALB/c mice were sensitized and challenged with OVA in the presence and absence of chronic low dose chlorine exposure of naturally vaporized gas of 5% sodium hypochlorite solution. Airway inflammation and AHR were evaluated by bronchoalveolar lavage (BAL) cell recovery and non-invasive phlethysmography, respectively. Real-time qPCR, Western blot assay, and ELISA were used to evaluate the mRNA and protein expressions of cytokines and other inflammatory mediators. Human A549 and murine epithelial (A549 and MLE12) and macrophage (AMJ2-C11) cells were used to define the responses to low dose chlorine exposure in vitro.
Results
Chronic low dose chlorine exposure significantly augmented airway inflammation and AHR in OVA-sensitized and challenged mice. The expression of Th2 cytokines IL-4 and IL-5 and proinflammatory cytokine IL-1β and IL-33 were significantly increased in OVA/Cl group compared with OVA group. The chlorine exposure also activates the major molecules associated with inflammasome pathway in the macrophages with increased expression of epithelial alarmins IL-33 and TSLP in vitro.
Conclusion
Chronic low dose exposure of chlorine aggravates allergic Th2 inflammation and AHR potentially through activation of inflammasome danger signaling pathways.
doi:10.1371/journal.pone.0106861
PMCID: PMC4159271  PMID: 25202911
21.  Myocardial Blood Flow and Flow Reserve in Proximal and Mid-to-Distal Lesions of Left Anterior Descending Artery Measured By N-13 Ammonia PET/CT 
Purpose
The purpose of this study is to compare the myocardial blood flow (MBF) and flow reserve (MFR) between proximal and mid-to-distal lesions of the left anterior descending artery (pLAD and mdLAD, respectively) using N-13 ammonia positron emission tomography/computed tomography (PET/CT).
Methods
Subjects were 11 patients (six men and five women, mean age 64.5 years) with known coronary artery disease (CAD) involving LAD studied by N-13 ammonia PET/CT. They were divided into two groups by the location of stenotic lesions, i.e. pLAD versus mdLAD. Global and regional MBF and MFR were measured and compared. Characteristics of perfusion defects including the number of involved segments, basal area involvement, location, size, and shape were also compared between the two groups.
Results
The regional MFR in mid-anterior segment was significantly lower in pLAD group (1.80 ± 0.35 vs 2.76 ± 1.13 for pLAD and mdLAD groups, respectively, p = 0.034), while global MFR was not different (2.10 ± 1.10 vs 2.34 ± 0.84). Both stress and rest MBF in LAD territories were not different in both groups. The size of the perfusion defects were significantly larger in pLAD group (44.0 ± 11.5 % vs 21.1 ± 15.8 %, p = 0.041). Other characteristics such as location, basal area involvement, and shape were not significantly different between two groups.
Conclusions
The proximal lesion makes lower MFR in the mid-anterior segment and larger perfusion defect in the LAD territory but comparable MBF compared with mdLAD lesion.
Electronic supplementary material
The online version of this article (doi:10.1007/s13139-013-0208-6) contains supplementary material, which is available to authorized users.
doi:10.1007/s13139-013-0208-6
PMCID: PMC4035192  PMID: 24900102
N-13 ammonia positron emission tomography; Myocardial blood flow; Myocardial flow reserve; Perfusion defect; Left anterior descending artery
22.  Capsaicin cough sensitivity is related to the older female predominant feature in chronic cough patients 
Purpose
The present study aimed to examine the age and gender distributions among chronic cough patients referred to a tertiary cough clinic in Korea, and to investigate clinical factors related to the demographic findings.
Methods
Study participants were unselectively recruited from adult chronic cough patients who attended the cough clinic for the first time during one year. To validate their representativeness, their age and gender distributions were compared to the entire chronic cough population, or with those presenting with other chronic disease. Data from the baseline investigations were analyzed to identify clinical factors related to the demographic findings.
Results
A total of 272 chronic cough patients were included. They had a middle-aged female predominant feature (mean age: 52.8±15.7 years and female 69.1%). Their age and gender distributions were almost identical to the entire chronic cough population, but were distinct from patients with hypertension. Among clinical factors, the older female predominance was associated with enhanced capsaicin cough sensitivity, and also with the presence of 'cough by cold air' symptom. Allotussia and laryngeal paresthesia were highly common in chronic cough patients, affecting 94.8% and 86.8% of them, respectively.
Conclusions
The present study demonstrated older female predominance among adult chronic cough patients attending a referral cough clinic in Korea. The demographic features were significantly associated with the capsaicin cough responses and also potentially with allotussia (particularly cold air as the trigger). These findings suggest a role of cough reflex sensitization in the pathophysiology of chronic cough in adults.
doi:10.4168/aair.2014.6.5.401
PMCID: PMC4161680  PMID: 25228996
Cough; respiratory hypersensitivity
23.  Clinical Features of Fixed Drug Eruption at a Tertiary Hospital in Korea 
Purpose
Fixed drug eruption (FDE) is characterized by a well-defined erythematous patch, plaque, or bullous eruption that recurs at the same site as the result of systemic exposure to a causative drug, and resolves with or without hyperpigmentation. This study was carried out to identify the common causative drugs and clinical features of FDE in Korea.
Methods
We reviewed electronic medical records of all patients diagnosed with FDE from January 2000 to December 2010 at a tertiary hospital in Korea.
Results
A total of 134 cases were diagnosed as FDE. The mean age was 35.9 years (range, 0-82 years) and 69 (51.5%) of the patients were male. The mean duration from the first event to attending hospital was 1.9 years (range, 1-20 years). The mean number of recurrences was 2.6 (1-10), and 72.6% of patients sought medical care after experiencing symptoms twice or more. Four patients (3.1%) needed hospitalization. The most common sites were the upper extremities (47.7%), followed by the lower extremities, face, abdomen, chest, buttocks and perineum. Clear documentation on the causative drugs was available for 38 patients (28.4%), and among these, non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen accounted for 71.1% of cases, and antibiotics accounted for 15.8%. Eighty patients (59.7%) underwent active treatment for FDE, and topical steroids were most frequently prescribed (43.3%), with systemic steroids used in 11.2% of patients.
Conclusions
NSAIDs and acetaminophen were the main causative agents of FDE, however, the causative agents were not assessed in 25% of patients.
doi:10.4168/aair.2014.6.5.415
PMCID: PMC4161682  PMID: 25228998
Fixed drug eruption; non-steroidal anti-inflammatory drug
25.  Evaluation of accuracy of B-spline transformation-based deformable image registration with different parameter settings for thoracic images 
Journal of Radiation Research  2014;55(6):1163-1170.
Deformable image registration (DIR) is fundamental technique for adaptive radiotherapy and image-guided radiotherapy. However, further improvement of DIR is still needed. We evaluated the accuracy of B-spline transformation-based DIR implemented in elastix. This registration package is largely based on the Insight Segmentation and Registration Toolkit (ITK), and several new functions were implemented to achieve high DIR accuracy. The purpose of this study was to clarify whether new functions implemented in elastix are useful for improving DIR accuracy. Thoracic 4D computed tomography images of ten patients with esophageal or lung cancer were studied. Datasets for these patients were provided by DIR-lab (dir-lab.com) and included a coordinate list of anatomical landmarks that had been manually identified. DIR between peak-inhale and peak-exhale images was performed with four types of parameter settings. The first one represents original ITK (Parameter 1). The second employs the new function of elastix (Parameter 2), and the third was created to verify whether new functions improve DIR accuracy while keeping computational time (Parameter 3). The last one partially employs a new function (Parameter 4). Registration errors for these parameter settings were calculated using the manually determined landmark pairs. 3D registration errors with standard deviation over all cases were 1.78 (1.57), 1.28 (1.10), 1.44 (1.09) and 1.36 (1.35) mm for Parameter 1, 2, 3 and 4, respectively, indicating that the new functions are useful for improving DIR accuracy, even while maintaining the computational time, and this B-spline-based DIR could be used clinically to achieve high-accuracy adaptive radiotherapy.
doi:10.1093/jrr/rru062
PMCID: PMC4229927  PMID: 25053349
deformable image registration; adaptive radiotherapy; 4DCT; lung

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