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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 1 (B = − 0.106 ± 0.106, P = 0.006) were negatively associated with length of hospital stay. In addition, DLCO showed better predictive ability than FEV1 in ROC curve analysis. The area under the curve (AUC) of DLCO was greater than 0.68 for all prognostic factors, and in contrast, the AUC of FEV1 was less than 0.68. Conclusion DLCO was likely to be as good as or better prognostic marker than FEV1 in severe AECOPD.

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). Conclusion 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 Current guidelines for the treatment of asthma and chronic obstructive pulmonary disease overlap (ACO) recommend initial treatment using inhaled corticosteroids (ICSs) plus 1 or more bronchodilators. Objective To clarify which therapeutic effect is better between the ICS + long-acting β2 agonist (LABA) and ICS + LABA + long-acting muscarinic antagonist (LAMA) treatment in patients with ACO. Methods We conducted a multicenter, 48-week, randomized, noninferiority trial. Patients with ACO were enrolled if they were treated with a moderate to high dose of ICS + LABA. In total, 303 patients were involved in the present trial, with 149 receiving ICS + LABA + LAMA. The primary end point was the time to first exacerbation. Secondary outcomes included changes in FEV1, forced vital capacity, FEV1/forced vital capacity ratio, asthma control, blood eosinophil count, and fractional exhaled nitric oxide. Results In the ICS + LABA treatment group, 29 of 154 patients (18.83%) experienced exacerbation, whereas 28 of 149 patients (18.79%) experienced exacerbation in the ICS + LABA + LAMA treatment group. The results of this noninferiority study were ultimately inconclusive (hazard ratio, 1.1; 95% CI, 0.66-1.84). However, the patients treated with the addition of LAMA showed significant improvements in FEV1 and forced vital capacity (P Conclusions Although this study was unable to conclude that ICS + LABA treatment is not inferior to ICS + LABA + LAMA in terms of exacerbation, it is obvious that the ICS + LABA + LAMA treatment group had improved lung function in ACO.

Quite a few patients with chronic spontaneous urticaria (CSU) are refractory to H₁-antihistamines, even though the dose of H₁-antihistamines is increased up to 4-fold. CSU that is not controlled with H₁-antihistamines results in increased disease burden. Several immunomodulators have been used to manage these patients. The guidelines reported herein are connected to Part 1 of the KAAACI/KDA Evidence-Based Practice Guidelines for Chronic Spontaneous Urticaria in Korean Adults and Children, and aimed to provide evidence-based recommendations for the management of H₁-antihistamine-refractory CSU. Part 2 focuses on the more commonly used additional treatment options for refractory CSU, including omalizumab, cyclosporine, leukotriene receptor antagonist, dapsone, methotrexate, and phototherapy. The evidence to support their efficacy, dosing, safety, and selection of these agents is systematically reviewed. To date, for patients with refractory CSU, the methodologically sound data to evaluate the use of omalizumab has been growing; however, the evidence of other immunomodulators and phototherapy is still insufficient. Therefore, an individualized stepwise approach with a goal of achieving complete symptom control and minimizing side effects can be recommended. Larger controlled studies are needed to elevate the level of evidence to select a rational therapeutic agent for patients with refractory CSU.

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.

Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Gyu Young Hur, Sung Yong Lee, Jae Jeong Shim, Kyung Ho Kang, Kyung Hoon Min Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Acute exacerbation of COPD (AECOPD) leads to rapid deterioration of pulmonary function and quality of life. It is unclear whether the prognosis for AECOPD differs depending on the bacterium or virus identified. The purpose of this study is to determine whether readmission of patients with severe AECOPD varies according to the bacterium or virus identified.Methods: We performed a retrospective review of medical records of 704 severe AECOPD events at Korea University Guro Hospital from January 2011 to May 2017. We divided events into two groups, one in which patients were readmitted within 30 days after discharge and the other in which there was no readmission.Results: Of the 704 events, 65 were followed by readmission within 30 days. Before propensity score matching, the readmission group showed a higher rate of bacterial identification with no viral identification and a higher rate of identification with the Pseudomonas aeruginosa (P=0.003 and P=0.007, respectively). Using propensity score matching, the readmission group still showed a higher P. aeruginosa identification rate (P=0.030), but there was no significant difference in the rate of bacterial identification, with no viral identification (P=0.210). In multivariate analysis, the readmission group showed a higher P. aeruginosa identification rate than the no-readmission group (odds ratio, 4.749; 95% confidence interval, 1.296–17.041; P=0.019).Conclusion: P. aeruginosa identification is associated with a higher readmission rate in AECOPD patients. Keywords: acute exacerbation of COPD, Pseudomonas aeruginosa, readmission, bacterium, virus

Patients with tuberculosis-destroyed lungs (TDLs), with airflow limitation, have clinical characteristics similar to those of patients with chronic obstructive pulmonary disease (COPD). Acute exacerbation is an important factor in the management of TDL. Therefore, the aim of this study was to investigate the factors associated with acute exacerbations in patients with stable TDL with airflow limitation.We evaluated the clinical characteristics, such as lung function, image findings, and serum laboratory findings, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and interleukin (IL)-6, in patients with TDL with chronic airflow limitation (n=94). We evaluated the correlation of these parameters with acute exacerbation.We found that patients with exacerbation were more likely to have bronchiectasis than those without exacerbation (patients with exacerbation, 66.7%; patients without exacerbation, 30.5%; P=0.001). CRP and IL-6 levels were significantly higher in patients with exacerbation than in those without exacerbation (P=0.001 and P0.001, respectively). Bronchiectasis [OR, 3.248; 95% confidence interval (CI), 1.063-9.928; P=0.039] and elevated IL-6 levels (OR, 1.128; 95% CI, 1.013-1.257; P=0.028) were the most important parameters associated with acute exacerbation in patients with TDL with airflow limitation.Patients with bronchiectasis and high IL-6 levels may require more intensive treatment to prevent acute exacerbation.

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Adnan Khan,4 Jinhyuk Na,4 Youngja H Park,4 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea; 4Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Republic of Korea Purpose: Asthma–COPD overlap (ACO) is heterogeneous in nature and requires a unified diagnostic approach. We investigated the urinary levels of L-histidine, a precursor of histamine related to inflammatory responses, as a new candidate biomarker for diagnosing this condition.Patients and methods: We performed a prospective multicenter cohort study with retrospective analysis of 107 patients, who were divided into three groups: asthma, COPD, and ACO, according to the Spanish guidelines algorithm. Urinary L-histidine levels were measured using liquid chromatography-mass spectrometry. High-resolution metabolomic analysis, coupled with liquid chromatography-mass spectrometry and followed by multivariate statistical analysis, was performed on urine samples to discriminate between the metabolic profiles of the groups.Results: Urinary L-histidine levels were significantly higher in patients with ACO than in those with asthma or COPD, but the subgroups of ACO, classified according to disease origin, did not differ significantly. High urinary L-histidine level was a significant factor for the diagnosis of ACO even after adjusting for age, sex, and smoking amount. Among patients with airflow obstruction, the urinary L-histidine levels were elevated in patients with a documented history of asthma before the age of 40 years or bronchodilator responsiveness ≥400 mL; bronchodilator responsiveness ≥200 mL of forced expiratory volume in 1 second and exceeding baseline values by 12% on two or more visits; blood eosinophil count ≥300 cells·mm−3; and frequent exacerbations (P < 0.05).Conclusion: Urinary l-histidine could be a potential biomarker for ACO, regardless of the diversity of diagnostic definitions used. Keywords: asthma, COPD, ACO, urinary L-histidine, metabolomics, inhaled corticosteroid&nbsp

Background Current asthma guidelines recommend stepping down controller treatment when the condition is well-controlled for a certain time. However, the optimal step-down strategy for well-controlled patients receiving a low-dose inhaled corticosteroid (ICS) with a long-acting β2-agonist (LABA) remains unclear. Objective This study was a randomized, open-label, three-arm, parallel pragmatic trial comparing two kinds of step-down approaches for maintaining treatment. Methods Adults with asthma who were aged 18 years or older, and who had been stable with low-dose ICS/LABA for at least 3 months, were enrolled. Subjects (n = 225) were randomly allocated into one of three groups (maintaining low-dose ICS/LABA [G1], discontinuing LABA [G2], and reducing ICS/LABA to once daily [G3]), and were observed for 6 months. The primary end point was a change in Asthma Control Test (ACT) scores between randomization and the final 6-month follow-up. Results The change in ACT was analyzed in the per-protocol population; noninferiority was not demonstrated in either step-down group compared with the maintenance group (95% confidence interval of the difference, G2 vs G1 = –1.40-0.55; G3 vs G1 = –1.19-0.77). Although over 90% of patients were fine, higher rates of treatment failure were observed in step-down groups (G1: 0%; G2: 9.46%; and G3: 9.09%; P = .027). There were no significant differences between step-down approaches in terms of ACT change or treatment failure. Conclusions Both step-down methods were not noninferior to maintenance of treatment. Step-down therapy can be attempted when patients are stable, but appropriate monitoring and supervision are necessary with precautions regarding loss of disease control.

PURPOSE OF REVIEW Respiratory allergies, including asthma and allergic rhinitis can also occur in the elderly. Allergen immunotherapy for allergic diseases is the only disease-modifying treatment for patients with allergies available thus far. Here, we review current evidence supporting the use of allergen immunotherapy in the elderly and discuss its efficacy and utility for the treatment of respiratory allergic diseases in this setting. RECENT FINDINGS Subcutaneous and/or sublingual immunotherapy are effective therapeutic options in not only young but also older patients. Allergen immunotherapy reduces medication and symptom scores in the elderly and can thus be safely prescribed in this population. SUMMARY Elderly individuals with proven, clinically relevant immunoglobulin E sensitization to inhalant allergens may benefit from allergen immunotherapy for respiratory allergic diseases. Older patients without contraindications should therefore be considered for treatment, with the additional benefit of reduced medication and symptom scores.

The tools for asthma control assessment recommended by the current guideline are cognitive function- and effort-dependent, which is substantially impaired in the elderly. The aim of this study is to investigate objective assessment tools of asthma control status and previous asthma exacerbation (AE) in elderly subjects. Asthmatics aged >60 years who were treated with step 2 or 3 by the Global Initiative for Asthma (GINA) guideline were enrolled. During the 12-week study period, the subjects used either 400 μg of budesonide plus 10 mg of montelukast or 800 μg of inhaled budesonide. The occurrence of AE during the 4-week run-in and 12-week treatment period was monitored. After 12-week of treatment, sputum eosinophil count, peripheral eosinophil count, the plasma leukotriene E4 (LTE4), and prostaglandin F2α (PGF2α) metabolite levels were measured using the UHPLC/Q-ToF MS system. The study subjects were divided into group 1 (asthmatics who experienced AE during the study period) and group 2 (those who did not). A total of 101 patients aged 60-85 years were enrolled. Twenty-three patients (22.8%) had experienced AE. The plasma LTE4 level, LTE4/PGF2α ratio, and peripheral eosinophil count were significantly higher in group 1 than in group 2 (P=0.023, P=0.010, P=0.033, respectively). The plasma LTE4/PGF2α ratio and peripheral eosinophil count at week 12 were significantly associated with previous AE (odds ratio [OR]=1.748, P=0.013; OR=1.256, P=0.027). Receiver operating characteristic (ROC) curves to discriminate the subjects with previous AE, including these 2 parameters, showed that the area under the curve was 0.700 (P=0.004), with 73.9% sensitivity and 47.9% specificity. In conclusion, a combination of plasma LTE4/PGF2α ratio and peripheral eosinophil count can be an objective assessment tool which is significantly associated with asthma control status in elderly asthmatics.

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.

Background The number of hypersensitivity reactions associated with iodinated contrast media (ICM) is increasing with widespread use of radiographic contrast agents. These hypersensitivity reactions are unpredictable and sometimes lead to severe reactions such as anaphylaxis. Objective To investigate the value of intradermal skin test (IDT) as a clinical screening tool for prediction of a hypersensitivity reaction to ICM. Methods We performed IDT in the patients scheduled to receive an iodinated contrast agent between September 2015 and April 2017. After IDT, the contrast agent tested was administered intravenously, regardless of the results of skin testing, and the patients were carefully monitored. Results We recruited 2,918 patients in 2 hospitals, and 2,843 were included in the final analysis. Fifteen (0.5%) of the 2843 patients had a positive IDT result before scheduled computed tomography scan; however, none of these patients experienced a hypersensitivity reaction after the administration of a full dose of ICM. Meanwhile, 19 patients who experienced hypersensitivity reactions after ICM challenge had showed a negative IDT result. The sensitivity and the positive predictive value of IDT for ICM were both 0%. Conclusions Routine IDT before the administration of an iodinated contrast agent does not predict hypersensitivity considering its extremely low sensitivity and a low positive predictive value.

Background Because severe cutaneous adverse reactions (SCARs), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) rarely occur, clinical data based on large-scale studies are still lacking. Objective To provide information on culprit drugs and clinical characteristics, including morbidity and mortality of SCARs based on a nationwide registry. Methods SCAR cases that occurred from 2010 to 2015 were recruited to the Korean SCAR registry from 34 tertiary referral hospitals. Demographics, causative drugs, causality, and clinical outcomes were collected by reviewing the medical record. Results A total of 745 SCAR cases (384 SJS/TEN cases and 361 DRESS cases) due to 149 drugs were registered. The main causative drugs were allopurinol (14.0%), carbamazepine (9.5%), vancomycin (4.7%), and antituberculous agents (6.3%). A strong preference for SJS/TEN was observed in carbonic anhydrase inhibitors (100%), nonsteroidal anti-inflammatory drugs (84%), and acetaminophen (83%), whereas dapsone (100%), antituberculous agents (81%), and glycopeptide antibacterials (78%) were more likely to cause DRESS. The mortality rate was 6.6% (SJS/TEN 8.9% and DRESS 4.2%). The median time to death was 19 days and 29 days in SJS/TEN and DRESS respectively, and 89.8% of deaths occurred within 60 days after the onset of the skin symptoms. Conclusion Allopurinol, carbamazepine, vancomycin, and antituberculous agents were the leading causes of SCARs in Korea. Some drugs preferentially caused a specific phenotype. The mortality rate of SCARs was 6.6%, and most of the deaths occurred within 2 months.

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 platinum-based 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.

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: Combined pulmonary fibrosis and emphysema (CPFE) is frequently associated with lung cancer. However, the impact and outcomes of lung cancer in patients with CPFE are unclear. Objective: We investigated the impact of lung cancer in patients with CPFE in terms of acute exacerbation (AE) and mortality, and identified the mortality predictors of patients with CPFE and lung cancer. Methods: We retrospectively reviewed 12-year medical records of patients at the Korea University Guro Hospital. Based on computed tomography findings, we selected CPFE patients with and without lung cancer, and analyzed age, sex, smoking status and history, body mass index, past medical history, pulmonary function, the gender, age, and physiology (GAP) score, AE, and mortality. Results: Of 227 CPFE patients, 61 were diagnosed with lung cancer. While 10 of the 61 patients experienced AE, 41 died during the observation period. Lung cancer was a significant predictor of AE (hazard ratio [HR] 3.27, 95% confidence interval [CI ]1.44–7.43, P

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-identification, 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

Benralizumab is an interleukin-5 receptor α-directed cytolytic monoclonal antibody that has been shown to safely reduce exacerbations and improve lung function for patients with asthma. We assessed the long-term safety and efficacy of benralizumab for patients with severe, uncontrolled eosinophilic asthma.We conducted a randomised, double-blind, parallel-group, phase 3 extension study at 447 sites in 24 countries. Eligible patients had to have completed the SIROCCO or CALIMA trials and remained on subcutaneous benralizumab 30 mg every 4 weeks (Q4W) or every 8 weeks (Q8W). Patients who had received placebo in those trials were re-randomised in a 1:1 ratio, using an interactive web-based system, to benralizumab 30 mg either Q4W or Q8W (first three doses 4 weeks apart). Treatment lasted for 56 weeks for adult patients (age ≥18 years) and 108 weeks for adolescent patients (age 12-17 years). The primary endpoint was the safety and tolerability of the two dosing regimens of benralizumab up to 68 weeks for adult patients (including the follow-up visit post-treatment) and up to 56 weeks for adolescent patients. This endpoint was assessed in the full analysis set, which included all patients from the SIROCCO and CALIMA predecessor studies who received at least one dose of study treatment in BORA and did not continue into another trial. This study is registered with ClinicalTrials.gov (NCT02258542).Between Nov 19, 2014, and July 6, 2016, we enrolled 1926 patients, of whom 633 had received benralizumab Q4W and 639 had received benralizumab Q8W in SIROCCO or CALIMA. The remaining 654 patients had received placebo in those trials and were randomly re-assigned in this trial to receive benralizumab Q4W (n=320) or Q8W (n=334). 1576 patients, including 783 who received benralizumab Q4W (265 newly assigned) and 793 who received benralizumab Q8W (281 newly assigned), were included in the full analysis set. The most common adverse events in all groups were viral upper respiratory tract infection (14-16%) and worsening asthma (7-10%). The most common serious adverse events were worsening asthma (3-4%), pneumonia (1% to 1%), and pneumonia caused by bacterial infection (0-1%). The percentages of patients who had any on-treatment adverse event, any serious adverse event, or any adverse event leading to treatment discontinuation during BORA were similar between patients originally assigned benralizumab and those originally assigned placebo and between benralizumab treatment regimens. The percentage of patients who had any adverse event was similar between SIROCCO or CALIMA (71-75%; benralizumab group only) and BORA (65-71%), as was the percentage of patients who had an adverse event that led to treatment discontinuation (2% in SIROCCO and CALIMA vs 2-3% in BORA).The 2 years of safety results validate that observations observed in the first year of benralizumab continued through a second year of treatment. No new consequences of long-term eosinophil depletion occurred, and the incidence of other adverse events, including opportunistic infections, were similar during the second year.AstraZeneca and Kyowa Hakko Kirin.

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Jeonju, Republic of Korea Purpose: Tuberculosis-associated COPD (T-COPD) has clinical characteristics similar to those of smoking-associated COPD (S-COPD), such as dyspnea, sputum production, and acute exacerbation (AE). However, the degree of systemic inflammation and prognosis might be different because of difference in the pathophysiology. The aim of this study was to compare the lung function, systemic inflammatory markers, and their impacts on AE in patients with S-COPD and T-COPD.Patients and methods: We performed a multicenter cross-sectional cohort study. We evaluated clinical characteristics, pulmonary function tests, levels of inflammatory markers, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IL-6, and the association of these markers with AE in patients with S-COPD and T-COPD.Results: Patients with T-COPD included more women and had lesser smoking history and higher St George Respiratory Questionnaire score than did patients with S-COPD. Although the FEV1 of both groups was similar, FVC, vital capacity, total lung capacity, and functional residual capacity were lower in patients with T-COPD than in those with S-COPD. CRP, ESR, and IL-6 levels were significantly higher in patients with T-COPD compared to patients with S-COPD. According to a multivariate logistic regression analysis, FEV1 was a significant factor predicting AE in S-COPD, and IL-6 was a significant factor predicting AE in T-COPD. IL-6 level greater than 2.04 pg/mL was a cutoff for predicting exacerbation of T-COPD (sensitivity 84.8%, specificity 59.3%, P

Jee Youn Oh,1 Young Seok Lee,1 Kyung Hoon Min,1 Gyu Young Hur,1 Sung Yong Lee,1 Kyung Ho Kang,1 Chin Kook Rhee,2 Seoung Ju Park,3 Jae Jeong Shim1 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Republic of Korea; 2Division of Pulmonary Medicine, Department of Internal Medicine, Catholic University Seoul Hospital, Seoul, Republic of Korea; 3Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Republic of Korea Purpose: Improvement in the diagnosis of asthma and chronic obstructive pulmonary disease (COPD) overlap (ACO), and identification of biomarkers for phenotype recognition will encourage good patient care by providing optimal therapy. We investigated club cell secretory protein (CC-16), a protective and anti-inflammatory mediator, as a new candidate biomarker for diagnosing ACO.Patients and methods: We performed a multicenter cohort study. A total of 107 patients were divided into three groups – asthma, COPD, and ACO – according to the Spanish guidelines algorithm, and enrolled into the study. Serum CC-16 levels were measured using commercial ELISA kits.Results: Serum CC-16 levels were the lowest in patients with ACO. Low serum CC-16 levels were a significant marker for the ACO even after adjustment for age, sex, and smoking intensity. Serum CC-16 levels were positively correlated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25%–75% of FVC, FEV1/FVC, vital capacity, and diffusing capacity of the lung for carbon monoxide, and were negatively correlated with smoking amount (pack-years), bronchodilator response, fractional residual capacity, residual volume, and number of exacerbations per year. FEV1 and serum CC-16 levels were significantly lower in patients with frequent exacerbations.Conclusion: Serum CC-16 has the potential to be a biomarker for ACO diagnosis and also treat frequent exacerbations in patients with chronic inflammatory airway diseases. Keywords: asthma, COPD, ACO, exacerbation, club cell secretory protein-16, smoking

PURPOSE Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but serious condition that systematically damages various internal organs through T-cell-mediated immunological drug reactions. We aimed to investigate whether clinical manifestations of DRESS syndrome differ according to culprit drugs. METHODS We retrospectively analyzed data from 123 patients with probable/definite DRESS syndrome based on the RegiSCAR criteria (January 2011 to July 2016). The data were obtained from the Korean Severe Cutaneous Adverse Reaction Registry. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre criteria. The culprit drugs were categorized as allopurinol, carbamazepine, anti-tuberculosis drug, vancomycin, cephalosporins, dapsone, and nonsteroidal anti-inflammatory drugs. RESULTS Differences were observed among culprit drugs regarding the frequencies of hepatitis (P

Combined pulmonary fibrosis and emphysema (CPFE) patients visit hospitals frequently due to acute exacerbations (AEs); however, the predictors of CPFE AE have not been comprehensively described in literature. Thus, we investigated the predicting factors of AE in CPFE patients. We retrospectively reviewed medical records from the past 12 years at Korea University Guro Hospital. We selected CPFE patients by computed tomography findings. Rapid deterioration (RD) was defined as acute worsening of dyspnea requiring hospitalization and the presence of newly developed radiologic abnormalities. AE was defined as RD with newly acquired bilateral pulmonary infiltrates without evidence of pulmonary infection or other known causes. We evaluated the following variables in CPFE patients: age, sex, smoking history and amount, body mass index, past medical history, pulmonary function test, gender, age, and physiology (GAP) score, and the presence of lung cancer. Among 227 CPFE patients, 108 had RD and 31 developed AE. The most common cause of RD was infection (n = 60, 55.6%) and 28.7% (n = 31) developed AE. Lung cancer [hazard ratio (HR), 3.274; 95% confidence interval (95% CI) 1.444–7.425; P

Juwhan Choi, Jee Youn Oh, Young Seok Lee, Kyung Hoon Min, Gyu Young Hur, Sung Yong Lee, Kyung Ho Kang, Jae Jeong Shim Division of Respiratory, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Republic of Korea Introduction: Particulate matter and air pollution in Korea are becoming worse. There is a lack of research regarding the impact of particulate matter on patients with COPD. Therefore, the purpose of this study was to investigate the effects of various air pollution factors, including particulate matter, on the incidence rate of severe acute exacerbations of COPD (AECOPD) events. Methods: We analyzed the relationship between air pollutants and AECOPD events that required hospitalization at Guro Hospital in Korea from January 1, 2015 to May 31, 2017. We used general linear models with Poisson distribution and log-transformation to obtain adjusted relative risk (RR). We conducted further analysis through the Comprehensive Air-quality Index (CAI) that is used in Korea. Results: Among various other air pollutants, particulate matter was identified as a major source of air pollution in Korea. When the CAI score was over 50, the incidence rate of severe AECOPD events was statistically significantly higher [RR 1.612, 95% CI, 1.065–2.440, P=0.024]. Additionally, the particulate matter levels 3 days before hospitalization were statistically significant [RR 1.003, 95% CI, 1.001–1.005, P=0.006]. Conclusion: Particulate matter and air pollution increase the incidence rate of severe AECOPD events. COPD patients should be cautioned against outdoor activities when particulate matter levels are high. Keywords: air pollution, particulate matter, air quality index, acute exacerbation, COPD

Background/Objective: The aim of this study was to evaluate the characteristics and prognostic factors of small cell lung cancer (SCLC) with bone metastases. We also investigated the characteristics and predictive factors of skeletal-related events (SREs) in these patients. Materials and Methods: Sixty-one patients who were first diagnosed with SCLC with bone metastases at our institution were included in this retrospective analysis. Results: The overall survival (OS) of patients with bone metastases was shorter than that of patients without bone metastases (4.13 vs. 6.17 months, p = 0.015). Poor Eastern Cooperative Oncology Group (ECOG) performance status (PS; ≥2) and higher serum alkaline phosphatase (ALP; above upper normal limit × 2) were independent poor prognostic factors (p = 0.027 for ECOG PS, p = 0.002 for ALP). More than 1 SRE occurred in 21 patients (34.4%). Cervical spine metastasis, thoracic spine metastasis, pelvic bone metastasis, more than 5 bone metastatic regions and higher serum lactate dehydrogenase were correlated with the occurrence of SREs. Thoracic spinal metastasis was a strong predictive factor for the occurrence of SREs (odds ratio = 5.475; 95% CI: 1.080-27.755). Conclusion: Our study demonstrates the poor prognosis of SCLC patients with bone metastases. Physicians should treat SCLC patients with bone metastases with caution.

Quercetin is a bioflavonoid known for antioxidation and antiproliferation activities. We demonstrated that quercetin inhibited cancer cell growth and sensitized cancer cells to gemcitabine treatment by promoting apoptosis via inhibiting heat shock protein 70 expression. Our results suggest that quercetin might have potential to increase sensitivity to chemotherapy and that heat shock protein 70 could be a new target for lung cancer treatment.Quercetin is a bioflavonoid with antiproliferative and proapoptotic activity in various cancer cells. However, little is known about the mechanism by which quercetin inhibits cancer growth or its potential role as a chemosensitizer in lung cancer cells. We investigated whether quercetin-induced inhibition of heat shock protein 70 (HSP70) is involved in its anticancer activity and whether it could modulate the responsiveness of lung cancer cells to chemotherapy.Various concentrations of quercetin and gemcitabine, either alone or in combination, were applied to lung cancer cells (A549 and H460 cells). We evaluated cell viability with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt assay, apoptotic activity by determining caspase-3 and caspase-9 activities, and HSP70 expression using Western blot analysis after treatment.Quercetin reduced cell viability and suppressed HSP70 expression in both cell lines dose-dependently. Adding a fixed quercetin dose enhanced gemcitabine-induced cell death, which was related to increased caspase-3 and caspase-9 activities. Combination treatment with quercetin and gemcitabine downregulated HSP70 expression more prominently than treatment with quercetin or gemcitabine alone.Quercetin-induced HSP70 inhibition was involved in growth inhibition and sensitization to chemotreatment in lung cancer cells. Quercetin might have potential as a chemosensitizer in lung cancer treatment.

Background: Despite the development of molecular research and targeted therapy, patients with wild-type epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) still receive platinum doublet chemotherapy as the standard first-line treatment. We investigated the efficacy of first-line regimens in patients with wild-type EGFR nonsquamous NSCLC. Methods: We retrospectively analyzed the efficacy of various platinum doublet regimens as first-line treatments. Between 2007 and 2013, a total of 165 patients with wild-type EGFR nonsquamous NSCLC were included in this study. Results: Seventy-one (43.0%) patients were treated with pemetrexed plus platinum (PP) and 94 (57.0%) with non-pemetrexed plus platinum (NPP). The overall response rate was not different between the PP- and NPP-treated groups (26.8 vs. 28.7%, respectively; p = 0.78). The median progression-free survival (PFS) and overall survival (OS) also showed no differences between the two treatment groups (p = 0.12 for PFS, p = 0.42 for OS). The median PFS and OS for the PP group were 4.6 months (95% CI, 3.8-5.4) and 18.7 months (95% CI, 11.7-25.8), respectively, and for the NPP group, they were 4.2 months (95% CI, 3.4-5.0) and 12.2 months (95% CI, 10.3-14.1), respectively. In the subgroup analysis, most subgroups showed no significant difference in PFS and OS between the two treatment groups. Conclusion: Our data showed that the efficacy of various platinum doublet regimens was similar in patients with wild-type EGFR nonsquamous NSCLC.

Malignant mesothelioma (MM) is a rare tumor associated with asbestos exposure. It typically presents as thickening or nodularity of the pleura, although it can also originate from other sites consisting of mesothelia and have manifestations other than thickening or nodularity. Several studies have implied that these different manifestations are associated with a different tumor biology. We report the case of a 54-year-old man with multiple fungating masses diagnosed as MM on histological examination.

PURPOSE This study aims to determine the efficacy and safety of house dust mite (HDM)-sublingual immunotherapy (SLIT) in elderly patients with AR. METHODS A total of 45 patients aged ≥ 60 years with HDM-induced AR who had ≥ 3 A/H ratio on skin prick test and/or ≥ 0.35 IU/L to both Dermatophagoides farinae and Dermatophagoides pteronyssinus by ImmunoCAP were enrolled in 4 university hospitals. To evaluate additional effects of HDM-SLIT, they were randomized to the SLIT-treated group (n = 30) or control group (n = 15). Rhinoconjunctivitis total symptom score (RTSS), rhinoscopy score, Korean rhinoconjunctivitis quality of life questionnaire, rhinitis control assessment test, asthma control test scores, and adverse reactions, were assessed at the first visit (V1) and after 1 year of treatment (V5); for immunological evaluation, serum levels of HDM-specific immunoglobulin A/IgE/IgG1/IgG4 antibodies and basophil response to HDMs were compared between V1 and V5 in both groups. RESULTS There were no significant differences in demographics, RTSS, skin reactivity to HDMs, or serum total/specific IgE levels to HDMs (P < 0.05, respectively) between the 2 groups. Nasal symptom score and RTSS decreased significantly at year 1 in the 2 groups (P < 0.05). There were no significant differences in percent decrease in nasal symptom score and RTSS at year 1 between the 2 groups (P < 0.05); however, rhinoscopic nasal symptom score decreased significantly in the SLIT-treated group (P < 0.05). Immunological studies showed that serum specific IgA levels (not specific IgE/IgG) and CD203c expression on basophils decreased significantly at V5 in the SLIT-treated group (P = 0.011 and P = 0.001, respectively), not in the control group. The control group required more medications compared to the treatment group, but there were no differences in adverse reactions. CONCLUSIONS It is suggested that HDM-SLIT for 1 year could induce symptom improvement and may induce immunomodulation in elderly rhinitis patients.

Chronic obstructive pulmonary disease (COPD) is a systemic progressive inflammatory disease resulting from an abnormal inflammatory response to noxious stimuli. Bronchiectasis is also a chronic inflammatory condition, usually caused by repetitive infections. However, it is not clear whether the inflammatory signaling pathways involved are the same in both diseases. Therefore, we here compared the markers and metabolites related to inflammation in COPD and in bronchiectasis to elucidate the pathological mechanisms. We compared markers and metabolites in patients with COPD and in those with bronchiectasis with airflow limitation. The levels of the following inflammatory biomarkers were assessed: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), interleukin (IL)-6, and club cell secretory protein (CC)-16. Additionally, high-resolution metabolomic evaluation was conducted to evaluate the differentially expressed metabolic signature of the two diseases. The ESR and CRP levels were significantly higher, and the levels of CC-16 and IL-6 tended to be higher, among patients with bronchiectasis than among those with COPD. In the metabolomics analysis, serum metabolites of biliverdin IX alpha (m/z: 565.24 [M+H-H2O]+) and L-carnitine (m/z: 184.09 [M+Na]+) were significantly upregulated in sera of bronchiectasis patients. In sera of COPD patients, the levels of nicotine (m/z: 163.12 [M+H]+) and N-acetyl serotonin (m/z: 201.102 [M+H-H2O]+) were significantly higher. Patients with bronchiectasis with airflow limitation had higher levels of inflammatory biomarkers (ESR and CRP) and markers indicating compensation for inflammatory damage (biliverdin IX alpha and L-carnitine), than did patients with COPD. Further treatments modulating the inflammatory process may be useful in patients with bronchiectasis.

The present study investigated the importance of comorbidity scores and clinical parameters in elderly patients with non-small cell lung cancer (NSCLC) not harboring epidermal growth factor receptor (EGFR) mutations who received second-line chemotherapy. The present study also compared the efficacy of tyrosine kinase inhibitor and cytotoxic chemotherapy as second-line treatment in elderly patients. The present study retrospectively reviewed the treatment of elderly patients with NSCLC (≥70 years old) who received second-line chemotherapy at Korea University Guro Hospital. Patients who had an EGFR mutation were excluded from the analysis. Between 2005 and 2013, 126 patients were included in the present study. The median progression-free survival (PFS) and overall survival (OS) for all patients who received second-line treatment were 2.47 months [95% confidence interval (CI), 2.08-2.86] and 8.63 months (95% CI, 5.99-11.28), respectively. A total of 52 patients (41.3%) were treated with tyrosine kinase inhibitor (TKI) and 74 (58.7%) were treated with chemotherapy. No difference was observed in the median PFS and OS between the TKI and chemotherapy groups (P=0.287 for PFS and P=0.374 for OS). The Charlson comorbidity index was not associated with survival, whereas a simplified comorbidity score and clinical factors, including poor performance status, short PFS of first-line chemotherapy, presence of brain metastasis and low serum albumin and sodium levels were significant prognostic factors in these elderly patients. Second-line chemotherapy was not beneficial to patients who had at least 3 of these factors and a median OS of 1.73 months, whereas patients who had less than 2 of these factors had a median OS of 11.50 months. For elderly lung cancer patients without EGFR mutations, clinical parameters were the most important factors affecting survival, rather than the types of drugs.

Background: Hereditary angioedema (HAE) is a genetically heterogeneous autosomal dominant disorder characterized by recurrent episodes of nonpruritic, nonpitting edema increasing after puberty. It can be fatal due to laryngeal or gastrointestinal (GI) involvement with varied and changing frequency of mortality according to studies published from the Western countries. Epidemiological and clinical data of HAE in Asian countries are sparse. We sought to examine the clinical characteristics of HAE patients in Korea. Methods: Patients diagnosed with HAE at 15 tertiary hospitals across the country until 2016 were retrospectively reviewed. Results: A total of 65 patients diagnosed with HAE by 2016 were identified. The prevalence of HAE was estimated at 1.3/1,000,000 in Korea. Of the 65 patients, 21 (32.3%) were males. A total of 90.8% patients had type I HAE, while the remaining 9.2% patients had type II HAE. The first symptom developed after 20 years in 73.8% of patients, with a mean age 28.4 ± 14.1 years. The age at diagnosis was 36.5 ± 15.8 years, with a mean time delay of 7.8 ± 10.5 years. While the face (82.3%) and extremities (upper 71.0%, lower 62.9%) were the most frequently involved, the GI tract was affected in 40.5% of Korean HAE patients. Prophylaxis was maintained in 62.5% of patients. There was no reported case of death from HAE so far. Conclusions: The clinical manifestation and severity of HAE may vary according to ethnicity. HAE is more infrequent and GI involvement is less likely in Korea compared with Western countries.