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Background/Aims The prognosis of patients with idiopathic pulmonary fibrosis (IPF) and respiratory failure requiring mechanical ventilation is poor. Therefore, mechanical ventilation is not recommended. Recently, outcomes of mechanical ventilation, including those for patients with IPF, have improved. The aim of this study was to investigate changes in the use of mechanical ventilation in patients with IPF and their outcomes over time. Methods This retrospective, observational cohort study used data from the National Health Insurance Service database. Patients diagnosed with IPF between January 2011 and December 2019 who were placed on mechanical ventilation were included. We analyzed changes in the use of mechanical ventilation in patients with IPF and their mortality using the Cochran-Armitage trend test. Results Between 2011 and 2019, 1,227 patients with IPF were placed on mechanical ventilation. The annual number of patients with IPF with and without mechanical ventilation increased over time. However, the ratio was relatively stable at approximately 3.5%. The overall hospital mortality rate was 69.4%. There was no improvement in annual hospital mortality rate. The overall 30-day mortality rate was 68.7%, which did not change significantly. The overall 90-day mortality rate was 85.3%. The annual 90-day mortality rate was decreased from 90.9% in 2011 to 83.1% in 2019 (p = 0.028). Conclusions Despite improvements in intensive care and ventilator management, the prognosis of patients with IPF receiving mechanical ventilation has not improved significantly.

The optimal management of hospital-presenting sepsis remains poorly understood. We investigated the initial management in patients presenting with sepsis in the general ward, the association between fluid resuscitation and clinical outcomes, and the factors affecting fluid resuscitation. A retrospective study was conducted on patients who presented with sepsis-induced hypotension in the general ward. Patients were divided into Less 30 (fluid resuscitation less than 30 mL/kg) and More 30 (fluid resuscitation 30 mL/kg or more) groups. Multivariable logistic regression analysis was performed. The median resuscitation fluid volume was 500 mL (9.2 mL/kg) and 2000 mL (35.9 mL/kg) in the Less 30 (n = 79) and More 30 (n = 11) groups, respectively. The intensive care unit (ICU) mortality was similar between the two groups (43.0% vs. 45.5%). Twenty-two patients received continuous renal replacement therapy (CRRT) in the Less 30 group, whereas none received it in the More 30 group (27.8% vs. 0%). Fluid resuscitation ≥30 mL/kg was not associated with ICU mortality. Low body weight and systolic blood pressure were associated with fluid resuscitation ≥30 mL/kg. Most hospital-presenting sepsis patients received less than 30 mL/kg of fluid, and fluid resuscitation was not associated with ICU mortality.

Background Cardiac dysfunction patients have long been considered at high risk of reintubation. However, it is based on past studies in which only conventional oxygen therapy was applied after extubation. We investigated association between cardiac dysfunction and reintubation rate in situation where high-flow nasal cannula (HFNC) was widely used during post-extubation period. Methods We conducted a retrospective observational cohort study of patients treated with HFNC after planned extubation in medical intensive care unit of single tertiary center. Patients were divided into normal function group (ejection fraction [EF] ≥45%) and cardiac dysfunction group (EF

The Korean Society of Radiology and Medical Guidelines Committee amended the existing 2016 guidelines to publish the “Korean Clinical Practice Guidelines for Adverse Reactions to Iodide Contrast for Injection and Gadolinium Contrast for MRI: The Revised Clinical Consensus and Recommendations (2022 Third Edition).” Expert members recommended and approved by the Korean Society of Radiology, the Korean Academy of Asthma, Allergy and Clinical Immunology, and the Korean Nephrology Society participated together. According to the expert consensus or systematic literature review, the description of the autoinjector and connection line for the infection control while using contrast medium, the acute adverse reaction, and renal toxicity to iodized contrast medium were modified and added. We would like to introduce the revised contents.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6–47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8–161.5, P = 0.024], and 3) initial ACT score

Abstract Background It is important to assess the prognosis of patients with chronic obstructive pulmonary disease (COPD) and acute exacerbation of COPD (AECOPD). Recently, it was suggested that diffusing capacity of the lung for carbon monoxide (DLCO) should be added to multidimensional tools for assessing COPD. This study aimed to compare the DLCO and forced expiratory volume in one second (FEV1) to identify better prognostic factors for admitted patients with AECOPD. Methods We retrospectively analyzed 342 patients with AECOPD receiving inpatient treatment. We classified 342 severe AECOPD patients by severity of DLCO and FEV1 (≤ vs. > 50% predicted). We tested the association of FEV1 and DLCO with the following outcomes: in-hospital mortality, need for mechanical ventilation, need for intensive care unit (ICU) care. We analyzed the prognostic factors by multivariate analysis using logistic regression. In addition, we conducted a correlation analysis and receiver operating characteristic (ROC) curve analysis. Results In multivariate analyses, DLCO was associated with mortality (odds ratio = 4.408; 95% CI 1.070–18.167; P = 0.040) and need for mechanical ventilation (odds ratio = 2.855; 95% CI 1.216–6.704; P = 0.016) and ICU care (odds ratios = 2.685; 95% CI 1.290–5.590; P = 0.008). However, there was no statistically significant difference in mortality rate when using FEV1 classification (P = 0.075). In multivariate linear regression analyses, DLCO (B = − 0.542 ± 0.121, P

Background Docetaxel is one of the standard treatments for advanced non-small cell lung cancer. Docetaxel is usually administered in a 3-week schedule, but there is significant toxicity. In this phase II clinical study, we investigated the efficacy and safety of a 4-weekly schedule of docetaxel monotherapy, as first-line chemotherapy for advanced squamous cell carcinoma in elderly lung cancer patients. Methods Patients with stage IIIB/ IV lung squamous-cell carcinoma age 70 or older, that had not undergone cytotoxic chemotherapy were enrolled. Patients received docetaxel 25 mg/m2 on days 1, 8, and 15, every 4 weeks. Primary endpoint was the objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity profiles. Results A total of 19 patients were enrolled. Among 19 patients, 17 were for evaluated efficacy and safety. In the intent-to-treat population, ORR and disease control rate (DCR) were 11.8% and 47.1%, respectively. In the response evaluable population, ORR was 16.7% and DCR was 66.7%. Median PFS and OS were 3.1 months and 3.3 months, respectively. There were three adverse grade 3/4 events. Grade 1 neutropenia was reported in one patient. Conclusion Our data failed to demonstrate efficacy of a 4-weekly docetaxel regimen, in elderly patients with a poor performance status. However, incidence of side effects, including neutropenia, was lower than with a 3-week docetaxel regimen, as previously reported.

Background Bronchoscopy is a useful diagnostic and therapeutic tool. However, the clinical use of high-flow nasal cannula (HFNC) in adults with acute respiratory failure for diagnostic and invasive procedures has not been well evaluated. We present our experiences of well-tolerated diagnostic bronchoscopy as well as cases of improved saturation in hypoxaemic patients after a therapeutic bronchoscopic procedure. Methods We retrospectively reviewed data of hypoxaemic patients who had undergone bronchoscopy for diagnostic or therapeutic purposes from October 2015 to February 2017. Results Ten patients (44–75 years of age) were enrolled. The clinical purposes of bronchoscopy were for diagnosis in seven patients and for intervention in three patients. For the diagnoses, we performed bronchoalveolar lavage in six patients. One patient underwent endobronchial ultrasonography with transbronchial needle aspiration of a lymph node to investigate tumour involvement. Patients who underwent bronchoscopy for therapeutic interventions had endobronchial mass or blood clot removal with cryotherapy for bleeding control. The mean saturation (SpO2) of pre-bronchoscopy in room air was 84.1%. The lowest and highest mean saturation with HFNC during the procedure was 95% and 99.4, respectively. The mean saturation in room air post-bronchoscopy was 87.4%, which was 3.3% higher than the mean room air SpO2 pre-bronchoscopy. Seven patients with diagnostic bronchoscopy had no hypoxic event. Three patients with interventional bronchoscopy showed improvement in saturation after the procedure. Bronchoscopy was well tolerated in all 10 cases. Conclusion This study suggests that the use of HFNC in hypoxaemic patients during diagnostic and therapeutic bronchoscopy procedures has clinical effectiveness.

Purpose. Particulate matter (PM) is increasing every year in Asia. It is not fully understood how the airway is affected when inhaling PM. We investigated the correlation between particulate matter with a diameter of less than 10 μm (PM10) and fractional exhaled nitric oxide (FeNO) to determine whether PM causes airway inflammation. Material and Methods. We analyzed patients who visited our outpatient clinic and tested FeNO from January 2016 to December 2017 at the Korea University Guro Hospital. PM10 data were provided by the government of the Republic of South Korea, and measuring station of PM10 is located 800 meters from the hospital. We analyzed the correlation between PM10 and FeNO by a Pearson correlation analysis and by a multivariate linear regression analysis. To identify the most correlated times, we analyzed the correlation between the FeNO and PM10 daily average from the day of visit to 4 days before visit. Results. FeNO positively correlated with PM10 at two days before hospital visit in the Pearson correlation (Pearson correlation coefficient = 0.057; P-value = 0.023) and in the multivariate linear regression analysis (B = 0.051, P-value = 0.026). If the PM10 increased by 100 μg/m3, the FeNO result was expected to rise to 8.3 ppb in healthy people without respiratory disease. Conclusion. The positive correlation was found in both healthy people and asthmatic patients. Therefore, PM10 can increase airway inflammation.

Objective: Unusual clinical course Background: Melanoma differentiation associated gene-5 antibody (MDA-5 Ab) is one of the diagnostic autoantibodies that appears in idiopathic inflammatory myopathies (IIMs). Unlike when other autoantibodies are positive, when this antibody is positive, there is less characteristic muscle involvement. However, this MDA-5 Ab-positive myopathy presents extremely rapid progression of interstitial lung disease, resulting in a high mortality rate. Previous studies reported that the prognosis of this lung disease will be determined by the titer and suggest that low titers of MDA-5 antibody can indicate a good prognosis in associated interstitial lung disease. Case Report: Our case describes a 55-year-old woman who presented with acute respiratory symptoms and dyspnea. After hospitalization, symptoms and chest imaging worsened rapidly, and the radiology image of lung disease featured interstitial changes not seen in typical infections. We treated the patient with a high-flow oxygen nasal cannula, empirical antibiotics, and a systemic steroid. While treatment for a disease of unknown cause was continued, low titer of MDA-5 antibody was identified. Conclusions: This case suggests 2 points to consider about non-infectious interstitial changes with acute respiratory distress syndrome. First, when treating rapidly progressing interstitial pneumonia of an unknown cause, it is recommended to consider lung involvement of MDA-5 Ab dermatomyositis. Second, a low titer of MDA-5 Ab can be associated with better prognosis in this MDA-5 Ab dermatomyositis-related lung disease. [ABSTRACT FROM AUTHOR]

Purpose: The most common cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is respiratory infection. Most studies of bacterial or viral cause in AECOPD have been conducted in Western countries. We investigated bacterial and viral identification rates in AECOPD in Korea. Materials and Methods: We reviewed and analyzed medical records of 736 cases of AECOPD at the Korea University Guro Hospital. We analyzed bacterial and viral identification rates and classified infections according to epidemiological factors, such as Global Initiative for Chronic Obstructive Lung Disease stage, mortality, and seasonal variation. Results: The numbers of AECOPD events involving only bacterial identification, only viral identification, bacterial-viral co-identi- fication, and no identification were 200 (27.2%), 159 (21.6%), 107 (14.5%), and 270 (36.7%), respectively. The most common infectious bacteria identified were Pseudomonas aeruginosa (13.0%), Streptococcus pneumoniae (11.4%), and Haemophilus influenzae (5.3%); the most common viruses identified were influenza virus (12.4%), rhinovirus (9.4%), parainfluenza virus (5.2%), and metapneumovirus (4.9%). The bacterial identification rate tended to be higher at more advanced stages of chronic obstructive pulmonary disease (p=0.020 overall, p=0.011 for P. aeruginosa, p=0.048 for S. pneumoniae). Staphylococcus aureus and Klebsiella pneumoniae were identified more in mortality group (p=0.003 for S. aureus, p=0.009 for K. pneumoniae). All viruses were seasonal (i.e., greater prevalence in a particular season; p<0.050). Influenza virus and rhinovirus were mainly identified in the winter, parainfluenza virus in the summer, and metapneumovirus in the spring. Conclusion: This information on the epidemiology of respiratory infections in AECOPD will improve the management of AECOPD using antibiotics and other treatments in Korea. [ABSTRACT FROM AUTHOR]

Purpose: To determine the social and clinical characteristics of immigrants with tuberculosis (TB) in South Korea. Materials and Methods: The registered adult TB patients who were diagnosed and treated in Korea Medical Centers from January 2013 to December 2015 were analyzed retrospectively. A total of 105 immigrants with TB were compared to 932 native Korean TB patients. Results: Among these 105 immigrants with TB, 86 (82%) were Korean-Chinese. The rate of drug-susceptible TB were lower in the immigrants group than in the native Korean group [odds ratio (OR): 0.46; 95% confidence interval (CI): 0.22-0.96, p=0.035]. Cure rate was higher in the immigrant group than in the native Korean group (OR: 2.03; 95% CI: 1.26-3.28, p=0.003). Treatment completion rate was lower in the immigrant group than in the native Korean group (OR: 0.50; 95% CI: 0.33-0.74, p=0.001). However, treatment success rate showed no significant difference between two groups (p=0.141). Lost to follow up (default) rate was higher in the immigrant group than in the native Korean group after adjusting for age and drug resistance (OR: 3.61; 95% CI: 1.36-9.61, p=0.010). There was no difference between defaulter and non-defaulter in clinical characteristics or types of visa among these immigrants (null p value). However, 43 TB patients with recent immigration were diagnosed as TB even though they had been screened as normal at the time of immigration. Conclusion: Endeavor to reduce the default rate of immigrants with TB and reinforce TB screening during the immigration process must be performed for TB infection control in South Korea. [ABSTRACT FROM AUTHOR]

Purpose: Reactive oxygen species modulator 1 (Romo1) is a key mediator of intracellular reactive oxygen species production. However, examination of the clinical usefulness of Romo1 in cancers has been limited. We evaluated the association of Romo1 expression with clinical outcomes in advanced non-small cell lung cancer (NSCLC) patients treated with platinumbased chemotherapy. Materials and Methods: Romo1 expression in tumor tissue was examined by immunohistochemistry and evaluated by histological score. Survival analyses were performed according to Romo1 expression and the association between Romo1 expression and clinical parameters was evaluated. Results: A total of 88 tumor specimens were analyzed. Significantly shorter median progression-free survival (PFS) was observed in the high Romo1 group compared with the low Romo1 group (4.5 months vs. 9.8 months, p < 0.001), and the median overall survival (OS) of the high Romo1 group was also significantly shorter than that of the low Romo1 group (8.4 months vs. 15.5 months, p < 0.001). Results: of multivariate analyses showed significant association of high Romo1 expression with both poor PFS (hazard ratio [HR], 2.75; 95% confidence interval [CI], 1.71 to 4.44) and poor OS (HR, 3.99; 95% CI, 2.36 to 6.74). Results: of the subgroup analysis showed a similar association regardless of tumor histology. Romo1 expression showed no association with any clinical parameter including age, sex, smoking status, stage, differentiation, or tumor histology. Conclusion: Romo1 overexpression was associated with poor response to treatment and shorter survival in advanced NSCLC patients treated with platinum-based chemotherapy. Romo1 could be a potential adverse predictive marker in this setting. [ABSTRACT FROM AUTHOR]

Purpose: Factor XIII (FXIII), a thrombin-activated plasma transglutaminase zy-mogen, is involved in cancer development and progression through a triggered coagulation pathway. The aim of this study was to examine whether FXIII activity levels differed in non-small cell lung cancer (NSCLC) patients according to histological types and TNM stage when compared with healthy subjects. Materials and Methods: Twenty-eight NSCLC patients and 28 normal controls who had been individually age-, gender-, body mass index-, smoking status-, and smoking amount-matched were enrolled: 13 adenocarcinomas, 11 squamous cell carcinomas, and four undifferentiated NSCLCs; four stage I, two stage II, 12 stage III, and 10 stage IV NSCLCs. FXIII activity was measured using fluorescence-based protein arrays. Results: The median FXIII activity level of the NSCLC group [24.2 Loewy U/mL, interquartile range (IQR) 14.9-40.4 Loewy U/mL] was significantly higher than that of the healthy group (17.5 Loewy U/ mL, IQR 12.6-26.4 Loewy U/mL) (p=0.01). There were no differences in FXIII activity between adenocarcinoma (median 18.6 Loewy U/mL) and squamous cell carcinoma (median 28.7 Loewy U/mL). NSCLC stage significantly influenced FXIII activity (p=0.02). The FXIII activity of patients with stage III NSCLC (median 27.3 Loewy U/mL, IQR 19.3-40.5 Loewy U/mL) was significantly higher than those of patients with stage I or II (median 14.0 Loewy U/mL, IQR 13.1-23.1 Loewy U/mL, p=0.04). FXIII activity was negatively correlated with aPTT in NSCLC patients (r=-0.38, p=0.04). Conclusion: Patients with advanced-stage NSCLC exhibited higher coagulation FXIII activity than healthy controls and early-stage NSCLC patients. [ABSTRACT FROM AUTHOR]

Purpose: Our previous study indicated that the presence of wheat-specific IgG1 and IgG4 antibodies was associated with work-related symptoms in workers exposed to wheat flour. We performed this study to investigate the genetic polymorphisms of β2-adrenergic receptors and wheat-specific antibodies in association with the clinical parameters of baker's asthma. Materials and Methods: In total, 379 subjects working in a single industrial bakery were enrolled in this study. The skin prick test was performed with common inhalant allergens and wheat flour extract. The presence of serum- specific IgE, IgG1, and IgG4 antibodies to wheat flour were determined by ELISA. Whole blood samples were obtained for genotype analysis. Subjects were genotyped with regard to five candidate single nucleotide polymorphisms (SNPs) of the β2-adrenergic receptor gene (ADRB2; -47 T>C, 46 A>G, 79 C>G, 252 G>A, and 523 C>A) using a single-base extension method. Results: No significant associations were observed between the genotype/allele frequencies of any of the SNPs tested and any clinical parameters. The haplotype of ADRB2 (GAA composed of 46 A>G, 252 G>A, and 523 C>A) was significantly associated with work-related symptoms (p<0.05). Moreover, in subjects with the AG or GG genotype at 46 A>G and haplotype [GAA] of ADRB2, the prevalence rates of wheat-specific IgG1 antibodies and lower respiratory symptoms increased significantly with exposure intensity (both p<0.05). Conclusion: The findings of the present study suggest that ADRB2 genetic polymorphism may contribute to the development of work-related symptoms in workers exposed to wheat flour, which can lead to baker's asthma. [ABSTRACT FROM AUTHOR]

Background: Although the pathogenesis of toluene diisocyanate (TDI)-induced occupational asthma (TDI-OA) is incompletely understood, several studies have suggested immunologic mechanisms, including specific IgE responses. A few studies have suggested human leukocyte antigen (HLA) associations with TDI-induced asthma in Western countries, but this is the first investigation of associations between HLA class I and II alleles and TDI-induced asthma patients in Asia, using high-resolution analysis. Methods: Patients with TDI-OA (n = 84), asymptomatic exposed controls (AECs, n = 47) and unexposed normal controls (NCs, n = 127) were enrolled. HLA class I and II genotyping was performed by the direct DNA sequencing analysis. Specific serum IgE antibodies to the vapor type TDI-albumin conjugate were measured by ELISA. Results: There was no significant association between the allele frequencies and the phenotype of TDI-OA. However, the frequency of the HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype was significantly higher in TDI-OA patients (19%) than in AEC (2.1%, p = 0.007, OR 4.429, CI 1.497–13.103) or NC (3.1%, p < 0.001, OR 7.235, CI 2.236–22.510) subjects, with statistical significance persisting after correction for multiple comparisons. DQB1*0402 was significantly associated with the presence of specific IgE to TDI-albumin conjugates in serum (p = 0.006, OR 4.552, CI 1.540–13.449). This p value remained significant after correction for multiple comparison. Conclusion: The HLA DRB1*1501-DQB1*0602-DPB1*0501 haplotype may be a genetic marker for the development of TDI-induced asthma in Koreans. Several HLA alleles that enhance specific IgE sensitization in exposed subjects are indicated. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Purpose: Combination treatment of inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) is widely used as a maintenance regimen for the management of asthma. This study evaluated the effect of the β2-adrenergic receptor (ADRB2) polymorphism on lung function and asthma control with regular use of combination treatment of an inhaled ICS plus LABA. Materials and Methods: 43 Korean asthmatics who were symptomatic despite regular ICS use for at least 3 months were enrolled. For a 2-week run-in period, they received ICS (budesonide 800 μg/day) plus terbutaline (5 μg prn). as needed. During the 24-week active treatment period, they received budesonide 160 μg and formoterol 4.5 μg b.i.d. as maintenance and rescue medication. Pulmonary function and quality of life scores were monitored every 8 weeks; morning/evening peak expiratory flow meter (PEFR) was recorded daily. Patients were genotyped for ADRB2 Arg16Gly using single base extension methodology. Results: During the run-in period, there were no significant between-group differences in lung function; after 8 weeks of active treatment, Arg/Arg patients had significantly higher forced expiratory volume in 1 secord (FEV1) and maximal mid-expiratory flow (MMEF) (p = 0.023 and p = 0.021, respectively), and better asthma control and quality of life after 24 weeks (p = 0.016 and p = 0.028, respectively). During treatment, there was a greater improvement in morning/evening PEFR in Arg/Arg patients. Conclusion: Asthmatic patients with the Arg/Arg genotype at codon 16 of ADRB2 achieve better asthma control with long-term regular use of combined budesonide and formoterol treatment, suggesting that the ADRB2 genotype may dictate choice of treatment strategy. [ABSTRACT FROM AUTHOR]

Adenoids are known as immunosecretory organs and those in atopic children present cellular and cytokine profiles different from those of non-atopic children. We hypothesized that locally produced total IgE and allergen-specific antibodies could be involved in the inflammatory responses in adenoid tissue. Local productions of total IgE and Dermatophagoides pteronyssinus (DP)-specific IgE, IgA, IgG1, and IgG4 antibodies were evaluated, as well as their relationships with the markers of allergic inflammation within adenoid tissue. Eighteen atopic subjects, who were sensitized to more than one common aeroallergen, and 22 non-atopic subjects undergoing adenotonsillectomy, were recruited. Immunoassays using adenoid tissue homogenate were performed to quantify the levels of total IgE, eosinophil cationic protein (ECP), and mast cell tryptase. DP-specific IgE, IgA, IgG1, and IgG4 antibodies, soluble IL-2 receptors (sIL-2R), soluble CD23 (sCD23), and IL-6 were measured by ELISA. All parameters measured in adenoid tissue homogenate were presented as a ratio to the albumin level found in the adenoid. Median level of total IgE in adenoid tissue homogenate was significantly higher in atopic individuals than in non-atopic individuals. Median values of DP-specific IgE and IgA antibodies were significantly higher in atopics than in non-atopics (p = 0.001, p = 0.006, respectively), while no differences were seen in DP-specific IgG1 and IgG4 antibodies. ECP and sCD23 levels in adenoid homogenate were significantly higher in atopics than in non-atopics (p = 0.026, p = 0.048, respectively), while no significant differences were noted in tryptase, sIL-2R, and IL-6 levels. The levels of DP-specific IgE, IgA, IgG1, and IgG4 antibodies in adenoid homogenate correlated significantly with ECP levels, but not with those of sIL-2R, sCD23, and IL-6. The presence of total IgE and DP-specific antibodies in adenoid tissue was confirmed to be more prominent in atopics. In conclusion, locally-produced total IgE and DP-specific antibodies may contribute to eosinophilic inflammation in adenoid tissue in atopic children. [ABSTRACT FROM AUTHOR]

Introduction: Chronic urticaria (CU), defined as the recurring incidence of wheals with or without angioedema for more than 6 weeks, is a common disorder associated with mast cell activation, degranulation, and histamine release. Considering the association between the CRTH2 gene and mast cells, we investigated the association of this gene polymorphism with the CU phenotype and antihistamine drug requirement in patients with CU. Materials & methods: Two groups consisting of 384 patients with CU and 231 patients as normal controls (NCs) were enrolled from the Department of Allergy and Rheumatology, Ajou University Hospital, Suwon, Korea. Two polymorphisms of the CRTH2 gene, -466T>C and -129C>A were genotyped using primer extension methods. Results: No significant differences were detected in the genotype and allele frequencies of the two CRTH2 polymorphisms between the CU and NC groups, and no significant associations were observed with clinical parameters, such as atopy status, serum total IgE, prevalence of autoantibodies and duration of CU. However, CU patients with homozygous TT genotypes had significantly higher dose requirements of antihistamines to control the CU symptoms (164.56 ± 115.62 vs 137.38 ± 90.15 loratadine equivalents, mg/week) than those with the CT and CC genotypes (p = 0.025). The luciferase activity was significantly enhanced in the construct containing CRTH2 466C compared with the -466T-containing construct (p < 0.001). Co-transfection experiments with GATA-3 (300 ng) and the -466T and -466C CRTH2 alleles revealed that the CRTH2 -466T allele produced a greater increase in induction of luciferase activity than the -466C allele (p < 0.001). Conclusion: The CRTH2 -466T>C gene polymorphism may not affect on the phenotype of CU, but contributes to the required dose of antihistamines in patients with CU. [ABSTRACT FROM AUTHOR]

Purpose: A possible involvement of autoimmune mechanism in the pathogenesis of bronchial asthma has been proposed. Recently, alpha-enolase protein was identified as a major autoantigen recognized by circulating IgG autoantibodies in patients with severe asthma. To evaluate a possible pathogenetic significance of these autoantibodies in severe asthma, isotype (IgG, IgA, IgM, and IgE) and IgG subclass (IgG1, IgG2, IgG3, and IgG4) distributions of autoantibodies to recombinant human alpha-enolase protein were analyzed. Patients and Methods: We examined serum samples from 10 patients with severe asthma and 7 patients with mild-to-moderate asthma, and 5 healthy controls by immunoblot analysis. Severe asthma was defined as patients having at least 1 severe asthmatic exacerbation requiring an emergency department visit or admission in the last year despite continuous typical therapies. Results: IgG1 was the predominant IgG subclass antibody response to alpha-enolase protein in patients with severe asthma. IgG1 autoantibody to alpha-enolase protein was detected in 7 of 10 patients with severe asthma (70%), 1 of 7 patients with mild-to-moderate asthma (14.3%), and none of 5 healthy controls (0%) (chi-square test; p < 0.05). IgA, IgM, and IgE autoantibodies to alpha-enolase protein could not be detected in patients with severe asthma. Conclusion: IgG1 subclass was the predominant type of autoantibody response to alpha-enolase protein in patients with severe asthma, suggests a possibility of IgG1 autoantibodymediated complement activation in the pathogenesis of severe asthma. [ABSTRACT FROM AUTHOR]

Food-dependent exercise-induced anaphylaxis is a unique form of food allergy. Recent studies indicate that gliadin is a major allergen in patients with wheat-dependent exercise-induced anaphylaxis (WDEIA). We evaluated the value of serum gliadin-specific IgE in the diagnosis of WDEIA, as well as the characteristics and digestibilities of the IgE-binding components of gliadin. We analyzed 32 adult subjects sensitized to wheat; 26 were asymptomatic sensitizers and 6 had WDEIA. Wheat flour and gliadin-specific IgE levels were measured, and corresponding receiver operator characteristics (ROC) curves were determined. Patients with WDEIA had higher levels of gliadin-specific IgE than patients without WDEIA (p = 0.003). The area under the ROC curve for gliadin-specific IgE was 0.872, which suggested this assay could be used as a supplementary test for the diagnosis of WDEIA. IgE immunoblot analyses of reactions to wheat and gliadin extracts were compared both with and without simulated gastric fluid (SGF) and intestinal fluid incubation (SIF). All six WDEIA patients had high IgE binding signals to 50 kDa of gliadin extract on IgE immunoblots. This binding was suppressed by SGF, although minimal inhibition was noted with SIF incubation. [ABSTRACT FROM AUTHOR]

Abstract Introduction  Although methylene diphenyl diisocyanate (MDI) is widely used in industries, there have been few studies of the pathogenic mechanisms of MDI-induced occupational asthma (MDI-OA). Methods  We performed immunohistochemical analyses, measured inflammatory mediators and cytokines, and quantified histamine release (HR) from peripheral basophils in MDI-OA patients. Thirteen MDI-exposed workers (five MDI-OA, two MDI-induced esoinophilic bronchitis, and six asymptomatic exposed controls, AEC) were enrolled. Results and Discussion  Immunochemical analyses indicated significantly increased anti-eosinophilic cationic protein-stained cells in MDI-OA patients as compared with controls (P P P P P  [ABSTRACT FROM AUTHOR]

Chronic urticaria (CU) associated with aspirin sensitivity, termed aspirin-intolerant CU (AICU), is a common condition in the general population. The genetic mechanism of AICU still is not fully understood. We investigated genetic polymorphisms of FcεR1β and FcεR1γ in patients with CU including AICU and aspirin-tolerant CU (ATCU) by analyzing the genotypes and haplotypes of four subsets of FcεR1 genes in association with various clinical parameters. Four polymorphisms of FcεR1 (FcεR1β –109T>C, FcεR1β E237G, FcεR1γ –237A>G, and FcεR1γ –54G>T) were genotyped in 119 AICU patients and compared with 154 patients with ATCU and 224 normal healthy controls (NCs). No significant differences were observed with respect to the allele and genotype frequencies of all four FcεR1 single-nucleotide polymorphisms (SNPs; p > 0.05) in CU including AICU and ATCU patients. However, two SNPs at FcεR1β E237G and FcεR1γ –237A>G were associated with atopy in AICU patients but not in ATCU. AICU patients with the AG/GG genotype of FcεR1β E237G and FcεR1γ –237G allele had a significantly higher frequency of atopy than those with the AA genotype (p = 0.02 and p = 0.040), respectively. The release of histamine from basophils induced by anti-IgE antibodies was significantly higher in AICU patients than in NCs and was increased in atopic patients compared with nonatopic patients (p = 0.006 and p = 0.007, respectively). The FcεR1β E237G and FcεR1γ –237T>G polymorphisms may be associated with the rate of atopy, which in turn could increase the release of histamine from basophils and may lead to the development of the AICU phenotype. [ABSTRACT FROM AUTHOR]

Abstract  The pathogenic mechanism of acetyl salicylic acid (ASA)-induced urticaria (AIU) is not fully understood. We compared the levels of neutrophil activation and related cytokines in patients with ASA-intolerant acute urticaria (AIAU) and ASA-intolerant chronic urticaria (AICU). A total of 51 patients with AIAU, 88 patients with AICU, and 102 normal controls (NC) were enrolled in this study. The serum levels of myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-18 were compared among the three groups. The serum levels of MPO were highest in the AIAU group, followed by the AICU and NC groups, and the serum levels of IL-18 were significantly higher in the AIAU and AICU groups than in NC group. Within the AIU groups, significant correlations were noted between the levels of MPO and IL-8, and IL-8 and IL-18. In conclusion, neutrophil activation, which was associated with the levels of IL-8 and IL-18 in the AIAU group, may be involved in the pathogenic mechanism of AIU. A role for IL-18 in the pathogenesis of AIU is also suggested. [ABSTRACT FROM AUTHOR]

The mechanisms of eosinophil activation in perennial allergic rhinitis (AR) are not fully understood but may be mediated by a series of inflammatory mediators, including locally produced specific antibodies. The aim of this study was to evaluate the role of locally produced allergen-specific antibodies in the nasal lavage fluid during the recruitment of inflammatory cells in AR. Thirteen patients with AR and a positive nasal provocation test (NPT) with Dermatophagoides pteronyssinus and 10 asymptomatic subjects, sensitized to D. pteronyssinus but who had a negative NPT were enrolled. Nasal lavage fluids were collected before and at 10, 30, and 60 minutes and 3, 6, and 24 hours after the NPT. Inflammatory cells were counted, and eosinophil cationic protein (ECP) and specific immunoglobulin E (IgE), IgG, and IgA antibodies were measured by enzyme-linked immunosorbent assay. After NPT, six subjects showed early responses and seven subjects showed dual responses. The eosinophil count and ECP level in lavage fluid were significantly increased after NPT in patients with positive NPTs, and these values were significantly higher than in the negative group. The specific IgA level in lavage fluid was increased after NPT in the positive group, and significant differences were noted for both the early and the late positive responses. Significant correlations were found between specific IgA and ECP levels in lavage fluid during early and late responses. Eosinophil recruitment occurred during both early and late responses after allergen exposure in perennial AR. Locally produced allergen-specific IgA (but not IgE or IgG) may be involved in eosinophil activation in both early and late responses. [ABSTRACT FROM AUTHOR]

Leukotriene overproduction is the major characteristic of aspirin-intolerant asthma (AIA). Most studies examining the molecular genetic mechanisms of AIA have focused on leukotriene-related genes, including ALOX5, LTC4S, TXA2R and prostanoid-receptor genes. One study suggested that the human leukocyte antigen (HLA) allele DPB1*0301 may be a genetic marker for the AIA phenotype in European and Asian populations, and HLA-DPB1*0301 has been suggested as a useful genetic marker for predicting more favorable responders to leukotriene-receptor antagonists for long-term management of AIA. Although several reports have indicated possible associations between genetic polymorphisms and variable responses to leukotriene modifiers in nonaspirin sensitive asthmatic patients, few have suggested relationships between such genetic polymorphisms and variable responses to asthma drugs in AIA patients. [ABSTRACT FROM AUTHOR]

Objectives: Leukotriene receptor antagonists (LTRA), such as montelukast, have been used as a first-line treatment for patients with aspirin-intolerant asthma (AIA). This study evaluated associations between the clinical requirement for LTRA and genetic polymorphisms of the ALOX5, LTC4S, COX-2, CysLTR1 and TBXA2R genes in the arachidonic acid cascade in the long-term management of 89 AIA patients from a Korean population. Methods: Asthma control status was monitored for 1 year with maintenance medications of inhaled corticosteroid and oral LTRA, and AIA patients were classified into three groups according to the mean montelukast dose required per month to maintain asthma control for 1 year: group I (≥200 mg montelukast/month; n = 37), group II (5-150 mg/month; n = 25) and group III (<5 mg/month; n = 27). Genetic polymorphisms in the arachidonic acid cascade were determined using a single-base extension method. Results: We found that there was a significant difference in the genotype frequency of the CysLTR1 promoter polymorphism -634C > T among the three groups (p = 0.007 for group I vs group II, p = 0.017 for group I vs group III), while there were no significant associations between LTRA requirements and polymorphisms of the other genes. The patients with the variant genotype (CT or TT) of the -634C = T CysLTR1 promoter polymorphism showed a higher expression level than those with the common genotype (CC). Conclusion: These findings indicate that the CysLTR1 promoter polymorphism is a useful genetic marker for predicting LTRA requirements in the long-term management of AIA patients. [ABSTRACT FROM AUTHOR]

Neutrophils are considered to play a central role in ventilator-induced lung injury (VILI). However, the pulmonary consequences of neutrophil accumulation have not been fully elucidated. Matrix metalloproteinase-9 (MMP-9) had been postulated to participate in neutrophil transmigration. The purpose of this study was to investigate the role of MMP-9 in the neutrophilic inflammation of VILI. Male Sprague-Dawley rats were divided into three groups: 1) low tidal volume (LVT), 7 ml/kg of tidal volume (VT); 2) high tidal volume (HVT), 30 ml/kg of VT; and 3) HVT with MMP inhibitor (HVT+MMPI). As a MMPI, CMT-3 was administered daily from 3 days before mechanical ventilation. Degree of VILI was assessed by wet-to-dry weight ratio and acute lung injury (ALl) scores. Neutrophilic inflammation was determined from the neutrophil count in the lung tissue and myeloperoxidase (MPO) activity in the bronchoalveolar lavage fluid (BALF). MMP-9 expression and activity were examined by immunohistochemical staining and gelatinase zymography, respectively. The wet-to-dry weight ratio, ALI score, neutrophil infiltration, and MPO activity were increased significantly in the HVT group. However, in the HVT+MMPI group, pretreatment with MMPI decreased significantly the degree of VILI, as well as neutrophil infiltration and MPO activity. These changes correlated significantly with MMP-9 immunoreactivity and MMP-9 activity. Most outcomes were significantly worse in the HVT+MMPI group compared with the LVT group. In conclusion, VILI mediated by neutrophilic inflammation is closely related to MMP-9 expression and activity. The inhibition of MMP-9 protects against the development of VILI through the downregulation of neutrophil-mediated inflammation. [ABSTRACT FROM AUTHOR]

The main etiologic factor for chronic bronchitis is cigarette smoke. Exposure to cigarette smoke is reported to induce goblet cell hyperplasia and mucus production. Mucin synthesis in airways has been reported to be regulated by the EGFR system. Peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the ligand-activated nuclear receptor superfamily. PPAR-γ is implicated in anti-inflammatory responses, but mechanisms underlying these varied roles remain ill-defined. Recently, reports have shown that upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) might be one of the mechanisms through which PPAR-γ agonists exert their anti-inflammatory actions. However, no data are available on the role of PPAR-γ in smoke-induced mucin production. In this study, we investigated the effect of PPAR-γ agonist (rosiglitazone) on smoke-induced mucin production in NCI-H292 cells. Exposure to cigarette smoke causes a significant decrease in PTEN expression and increases dose-dependent EGFR-specific tyrosine phosphorylation, resulting in MUC5AC mucin production in NCI-H292 cells. PPAR-γ agonists or specific inhibitors of phosphoinositide 3-kinase exert inhibition of cigarette smoke-induced mucin production, with the upregulation of PTEN signaling and doworegulation of Akt expression. This study demonstrates that PPAR-γ agonist functions as a regulator of epithelial cell inflammation that may result in reduction of mucin-producing cells in airway epithelium. [ABSTRACT FROM AUTHOR]

Eperisone and afloqualone act by relaxing both skeletal and vascular smooth muscles to improve circulation and suppress pain reflex. These drugs are typically prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) as painkillers. However, there have been no reports on serious adverse reactions to oral muscle relaxants; and this is the first report to describe three allergic reactions caused by eperisone and afloqualone. All three patients had histories of allergic reactions after oral intake of multiple painkillers, including oral muscle relaxants and NSAIDs, for chronic muscle pain. An open-label oral challenge test was performed with each drug to confirm which drugs caused the systemic reactions. All patients experienced the same reactions within one hour after oral intake of eperisone or afloqualone. The severity of these reactions ranged from laryngeal edema to hypotension. To confirm that the systemic reaction was caused by eperisone or afloqualone, skin prick testing and intradermal skin tests were performed with eperisone or afloqualone extract in vivo, and basophil activity tests were performed after stimulation with these drugs in vitro. In one patient with laryngeal edema, the intradermal test with afloqualone extract had a positive result, and CD63 expression levels on basophils increased in a dose-dependent manner by stimulation with afloqualone. We report three allergic reactions caused by oral muscle relaxants that might be mediated by non-immunoglobulin E-mediated responses. Since oral muscle relaxants such as eperisone and afloqualone are commonly prescribed for chronic muscle pain and can induce severe allergic reactions, we should prescribe them carefully. [ABSTRACT FROM AUTHOR]

Polyethylene glycol (PEG)-electrolyte solution (Golytely), is most commonly used for bowel preparation before colonoscopy, as well as for barium enema and colon surgery. In this case, a 70-year-old man developed ARDS following the administration of Golytely by mouth before a scheduled colonoscopy. Aspiration of PEG-electrolyte solution was suspected, and the patient was successfully treated by BAL. Therefore, early bronchoscopy and BAL should be considered as initial treatment for PEG aspiration, because removal of PEG is most important for managing the disease. [ABSTRACT FROM AUTHOR]

The genetic mechanism of aspirin intolerant acute urticaria (AIAU) is unknown. To demonstrate an association between the β2 adrenergic receptor (ADRB2) polymorphism and the phenotype of AIAU, one hundred fourteen patients with AIAU, 110 patients with aspirin intolerant chronic urticaria (AICU), and 498 normal healthy controls (NC) based on a Korean population were enrolled. The genotype of ADRB2 at 46 A > G was analyzed using a direct sequencing method. The ADRB2 polymorphism at 46 A > G showed a significant difference between AIAU and NC; the frequency of the major genotype was significantly higher in the AIAU group (p = 0.017 in recessive model), while no differences were noted in allele and genotype frequencies between AICU and NC. In conclusion, the ADRB2 (46 A > G) gene polymorphism may contribute to the development of the phenotype of AIAU. [ABSTRACT FROM AUTHOR]

Mediastinal haemangioma is a rare disease. We report a 23-year-old male patient with a posterior mediastinal cavernous haemangioma. The CXR revealed a progressively enlarging mediastinal mass which on chest CT and angiography appeared to be a well-enhanced hypervascular tumour. Angiographic gel foam embolization of the feeding vessels was undertaken prior to the surgical removal of the mass. The mass lesion following surgical removal was shown to be a cavernous haemangioma on histological examination. [ABSTRACT FROM AUTHOR]

Asthma is characterized by airway obstruction and inflammation, and presents significant diagnostic and treatment challenges. The concept of endotypes has improved understanding of the mechanisms of asthma and has stimulated the development of effective treatment strategies. Sputum profiles may be used to classify asthma into two major inflammatory types: type 2-high (T2H) and type 2-low (T2L) asthma. T2H, characterized by elevated type 2 inflammation, has been extensively studied and several effective biologic treatments have been developed. However, managing T2L is more difficult due to the lack of reliable biomarkers for accurate diagnosis and classification. Additionally, conventional anti-inflammatory therapy does not completely control the symptoms of T2L; therefore, further research is needed to identify effective biologic treatments. This review provides new insights into the clinical characteristics and underlying mechanisms of severe T2L and investigates potential therapeutic approaches to control the disease.

Background/Aims Asthma is not a single disease but, rather, a heterogeneous inf lammatory disorder with various pathogenic mechanisms. We analyzed the associations between the cellular profile of sputum and the serum levels of inflammatory mediators/cytokines in a cohort of adult asthmatics. Methods We recruited 421 adult asthmatic patients. All subjects were classified into four groups according to their sputum cellular profiles: G1, eosinophilic; G2, mixed granulocytic; G3, neutrophilic; and G4, paucigranulocytic. Serum levels of cytokines and mediators including periostin, eosinophil-derived neurotoxin (EDN), S100A9, and folliculin were quantified. Results Among 421 patients, G1 accounted for 149 (35.4%), G2 for 71 (16.9%), G3 for 155 (36.8%), and G4 for 46 (10.9%). Serum periostin and EDN levels were significantly higher in G1 (p = 0.004, and p = 0.031) than in the others. Serum S100A9 levels were elevated in G2 and G3 (p = 0.008). Serum folliculin levels differed significantly among the four groups, with the highest level in G4 (p = 0.042). To identify G1 from G1 plus G2 groups, the optimal serum cut-off levels were 1.71 ng/mL for periostin, and 1.61 ng/mL for EDN. When these two parameters were combined, the sensitivity was 76.0% and the specificity was 64.3% (area under the curve, 0.701; p = 0.004). Conclusions The serum periostin and EDN levels may be used as predictors to discriminate the eosinophilic asthma group from patients having eosinophilic or mixed granulocytic asthma, and the serum folliculin level is significantly elevated in patients with paucigranulocytic asthma compared to those with different inflammatory cell profile.

Background: Although the prevalence of anaphylaxis is increasing worldwide, the large-scale studies in Asia evaluating anaphylaxis in all age groups are limited. We aimed to collect more precise and standardized data on anaphylaxis in Korea using the first multicenter web-based registry. Methods: Twenty-two departments from 16 hospitals participated from November 2016 to December 2018. A web-based case report form, designed by allergy specialists, was used to collect anaphylaxis data. Results: Within the 2-year period, 558 anaphylaxis cases were registered. The age of registered patients ranged from 2 months to 84 years, and 60% were aged

Background The pathogenic mechanisms of toluene diisocyanate (TDI)-induced asthma are not understood clearly.Methods In this review, we summarized recent data to further understand the pathogenic mechanisms through recent approach of molecular genetic studies, and specific antibody responses to cellular mechanisms.Results Genetic polymorphism studies suggested the involvement of oxidant/antioxidant-related genes and neurogenic inflammatory response genes. A high-resolution technique of HLA allele suggested some HLA genetic markers presenting the phenotype of TDI-induced asthma. The new volatile type of TDI-human serum albumin conjugate could improve specific immunoglobulin E and immunoglobulin G bindings in enzyme-linked immunosorbent assay studies for identifying TDI-induced asthma patients. The role of bronchial epithelial cells and cytokeratins derived from epithelial cells could be involved in autoantibody productions, suggesting that an autoimmune mechanism may be involved in airway inflammation. Neutrophil activation and oxidant/antioxidant-related mechanisms were also suggested.Conclusion The pathogenic mechanism of TDI-induced asthma is complicated as various humoral and cellular mechanisms are combined and involved differently on an individual basis. Therefore, additional efforts for further elucidation should follow. Keywords: asthma, genetic polymorphism, HLA, specific IgE, specific IgG, toluene diisocyanate

Objectives Reactive oxygen species modulator 1 (Romo1) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. Romo1 is increased in most cancer cell lines and is related with resistance to chemotherapy in vitro. However, data on its expression in patients with malignancy is very limited. We evaluated the usefulness of serum Romo1 as a potential diagnostic biomarker in non-small cell lung cancer (NSCLC). Materials and methods We initially assessed the expression of Romo1 using Western blotting and enzyme-linked immunosorbent assay in paired lung tissue and serum specimen from NSCLC patients who underwent surgical resection. Then we evaluated and compared serum Romo1 level in a healthy population (n=55), patients with benign lung diseases (n=63) and NSCLC patients (n=58). We explored the correlation between Romo1 expression and clinical parameters and assessed diagnostic performance of serum Romo1 for NSCLC using receiver operating characteristic (ROC) curve analysis. Results Romo1 expression in lung cancer tissues was significantly increased compared with non-tumorous tissues (p<0.001). Romo1 expression in cancer tissues positively correlated with that in serum (r=0.68, p=0.009). Serum Romo1 level in NSCLC patients significantly increased compared with that of healthy population or patients with benign lung diseases (both p<0.001). ROC curve analysis using an optimal cutoff value of 329.7pg/mL revealed sensitivity and specificity for the diagnosis of NSCLC of 81.9% and 89.8%, respectively, with an area under the curve of 0.847 (95% confidence interval: 0.789-0.892, p<0.001). Serum Romo1 level was not related with age, gender, smoking status, tumor differentiation, histological type or stage. Conclusions Serum Romo1 discriminated NSCLC patients from the population without cancer with considerable sensitivity and specificity. Serum Romo1 could be a potential diagnostic biomarker for NSCLC. [ABSTRACT FROM AUTHOR]