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Background: S100A8 and S100A9 have been gaining recognition for modulating tumor growthand metastasis. This study aimed at evaluating the clinical significance of S100A8 and S100A9 innon-small cell lung cancer (NSCLC)., Methods: We analyzed the relationship between S100A8and S100A9 expressions, clinicopathological characteristics, and prognostic significance in tumorcells and peritumoral inflammatory cells., Results: The positive staining of S100A8 in tumorcells was significantly increased in male (p < .001), smoker (p = .034), surgical method other thanlobectomy (p = .024), squamous cell carcinoma (SQCC) (p < .001) and higher TNM stage (p = .022)compared with female, non-smoker, lobectomy, adenocarcinoma (ADC), and lower stage. Theproportion of tumor cells stained for S100A8 was related to histologic type (p < .001) and patientsex (p = .027). The proportion of inflammatory cells stained for S100A8 was correlated with patientage (p = .022), whereas the proportion of inflammatory cells stained for S100A9 was correlatedwith patient sex (p < .001) and smoking history (p = .031). Moreover, positive staining in tumorcells, more than 50% of the tumor cells stained and less than 30% of the inflammatory cellsstained for S100A8 and S100A9 suggested a tendency towards increased survivability in SQCCbut towards decreased survivability in ADC., Conclusions: S100A8 and S100A9 expressions might be potential prognostic markers in patients with NSCLC.

Purpose: The microbial environment is an important factor that contributes to the pathogenesis of atopic dermatitis (AD). Recently, it was revealed that not only bacteria itself but also extracellular vesicles (EVs) secreted from bacteria affect the allergic inflammation process. However, almost all research carried out so far was related to local microorganisms, not the systemic microbial distribution. We aimed to compare the bacterial EV composition between AD patients and healthy subjects and to experimentally find out the beneficial effect of some bacterial EV composition., Methods: Twenty-seven AD patients and 6 healthy control subjects were enrolled. After urine and serum were obtained, EVs were prepared from samples. Metagenomic analysis of 16s ribosomal DNA extracted from the EVs was performed, and bacteria showing the greatest difference between controls and patients were identified. In vitro and in vivo therapeutic effects of significant bacterial EV were evaluated with keratinocytes and with Staphylococcus aureus-induced mouse AD models, respectively., Results: The proportions of Lactococcus, Leuconostoc and Lactobacillus EVs were significantly higher and those of Alicyclobacillus and Propionibacterium were lower in the control group than in the AD patient group. Therefore, lactic acid bacteria were considered to be important ones that contribute to the difference between the patient and control groups. In vitro, interleukin (IL)-6 from keratinocytes and macrophages decreased and cell viability was restored with Lactobacillus plantarum-derived EV treatment prior to S. aureus EV treatment. In S. aureus-induced mouse AD models, L. plantarum-derived EV administration reduced epidermal thickening and the IL-4 level., Conclusions: We suggested the protective role of lactic acid bacteria in AD based on metagenomic analysis. Experimental findings further suggest that L. plantarum-derived EV could help prevent skin inflammation., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Purpose: Severe asthma and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) are difficult to control and are often associated with poor clinical outcomes. However, much is not understood regarding the diagnosis and treatment of severe asthma and ACOS. To evaluate the current perceptions of severe asthma and COPD among asthma and COPD specialists, we designed an e-mail and internet-based questionnaire survey., Methods: Subjects were selected based on clinical specialty from among the members of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Academy of Tuberculosis and Respiratory Diseases. Of 432 subjects who received an e-mail invitation to the survey, 95 subjects, including 58 allergists and 37 pulmonologists, responded and submitted their answers online., Results: The specialists estimated that the percentage of severe cases among total asthma patients in their practice was 13.9%±11.0%. Asthma aggravation by stepping down treatment was the most common subtype, followed by frequent exacerbation, uncontrolled asthma despite higher treatment steps, and serious exacerbation. ACOS was estimated to account for 20.7% of asthma, 38.0% of severe asthma, and 30.1% of COPD cases. A history of smoking, persistently low forced expiratory volume in 1 second (FEV1), and low FEV1 variation were most frequently classified as the major criteria for the diagnosis of ACOS among asthma patients. Among COPD patients, the highly selected major criteria for ACOS were high FEV1 variation, positive bronchodilator response, a personal history of allergies and positive airway hyperresponsiveness. Allergists and pulmonologists showed different assessments and opinions on asthma phenotyping, percentage, and diagnostic criteria for ACOS., Conclusions: Specialists had diverse perceptions and clinical practices regarding severe asthma and ACOS patients. This heterogeneity must be considered in future studies and strategy development for severe asthma and ACOS., Competing Interests: There are no financial or other issues that might lead to conflict of interest., (Copyright © 2018 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease.)

Background: H1N1 influenza virus prevailed throughout the world in 2009. However, there are few reports on the clinical features of H1N1 influenza infection in adult asthma patients. We evaluated the clinical features in asthma patients with H1N1 influenza infection who took oseltamivir and compared them to those with other upper respiratory infections., Methods: We reviewed asthma patients over 15 years of age who had visited Seoul National University Hospital and Seoul National University Bundang Hospital for suspected H1N1 influenza infection from August 2009 to March 2010. Various clinical features such as hospital admission days, respiratory symptoms, basal lung function, and past history was compared between H1N1 influenza PCR positive and negative groups., Results: A total of 111 asthmatics were enrolled. All patients took oseltamivir. H1N1 RT-PCR was positive in 62 patients (55.9%), negative in 49 patients (44.1%). Wheezing developed more frequently in the H1N1 positive group. (43.5 vs. 16.7%, P=0.044). The rate of acute asthma exacerbations and pneumonia development were higher in the H1N1 positive group (59.7 vs. 51%, P=0.015, 25.0% vs. 0%, P<0.001). The rates for emergency room visit, hospital admissions, intensive care unit admissions, hospital days were not different between the groups. Underlying medical conditions were accompanied more frequently in the H1N1 negative patients (21.6% vs. 30.6%, P=0.002), especially cardiac disease (7.2% vs. 15.3%, P=0.011)., Conclusions: H1N1 influenza infection may affect the clinical course of asthma combined with more severe manifestations; however, Oseltamivir could have affected the clinical course of H1N1 infected patients and made it milder than expected.

Background: Anaphylaxis is a life-threatening allergic reaction. Several studies reported different anaphylactic reactions according to the causative substances. However, a comparison of anaphylaxis for each cause has not been done. This study was conducted to identify common causes of anaphylaxis, characteristics of anaphylactic reaction for each cause and to analyze the factors related to the severity of the reaction., Methods: Medical records of patients who visited the emergency room of Ewha Womans University Mokdong Hospital from March 2003 to April 2016 and diagnosed with anaphylactic shock were retrospectively reviewed. We compared the clinical features of anaphylaxis according to the cause. In addition, the severity of anaphylaxis was analyzed and contributing factors for severe anaphylaxis were reviewed., Results: A total of 199 patients with anaphylaxis were analyzed. Food was the most common cause (49.7%), followed by drug reaction (36.2%), bee venom (10.1%), and unknown cause (4.0%). Cardiovascular symptoms of syncope and hypotension were more common in drug-induced anaphylaxis. The incidence of severe anaphylaxis was the highest in anaphylaxis due to drugs (54.2%). Urticaria and other skin symptoms were significantly more common in food-induced anaphylaxis. Risk factors for severe anaphylaxis included older age, male, and drug-induced one. Epinephrine treatment of anaphylaxis was done for 69.7% and 56.9% of patients with food-induced and drug-induced anaphylaxis, respectively., Conclusions: More severe anaphylaxis developed with drug treatment and in males. Low rate of epinephrine prescription was also observed. Male patients with drug induced anaphylaxis should be paid more attention., (Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Background: Individual studies have suggested the utility of fractional exhaled nitric oxide (Feno) measurement in detecting cough-variant asthma (CVA) and eosinophilic bronchitis (EB) in patients with chronic cough., Objective: We sought to obtain summary estimates of diagnostic test accuracy of Feno measurement in predicting CVA, EB, or both in adults with chronic cough., Methods: Electronic databases were searched for studies published until January 2016, without language restriction. Cross-sectional studies that reported the diagnostic accuracy of Feno measurement for detecting CVA or EB were included. Risk of bias was assessed with Quality Assessment of Diagnostic Accuracy Studies 2. Random effects meta-analyses were performed to obtain summary estimates of the diagnostic accuracy of Feno measurement., Results: A total of 15 studies involving 2187 adults with chronic cough were identified. Feno measurement had a moderate diagnostic accuracy in predicting CVA in patients with chronic cough, showing the summary area under the curve to be 0.87 (95% CI, 0.83-0.89). Specificity was higher and more consistent than sensitivity (0.85 [95% CI, 0.81-0.88] and 0.72 [95% CI, 0.61-0.81], respectively). However, in the nonasthmatic population with chronic cough, the diagnostic accuracy to predict EB was found to be relatively lower (summary area under the curve, 0.81 [95% CI, 0.77-0.84]), and specificity was inconsistent., Conclusions: The present meta-analyses indicated the diagnostic potential of Feno measurement as a rule-in test for detecting CVA in adult patients with chronic cough. However, Feno measurement may not be useful to predict EB in nonasthmatic subjects with chronic cough. These findings warrant further studies to validate the roles of Feno measurement in clinical practice of patients with chronic cough., (Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background/aims: The Cough Symptom Score (CSS) is a simple, useful tool for measuring cough severity. However, there is no standard Korean version of the CSS. We developed a Korean version of the CSS and evaluated its clinical utility and validity for assessing chronic cough severity., Methods: The CSS was adapted for Korean use following a forward-backward translation procedure. Patients with chronic cough enrolled from five university hospitals were graded using the CSS and a 100-mm linear visual analog scale (VAS) of cough severity at each visit. Patients completed the Leicester Cough Questionnaire (LCQ) upon presentation and completed the LCQ and Global Rating of Change at follow-up visits after 2 to 4 weeks. The concurrent validity, repeatability, and responsiveness of the Korean version of the CSS were determined., Results: Correlation coefficients between the CSS and LCQ, and between the CSS and VAS, were -0.66 and 0.52, respectively. There was a weak correlation between the scores for night and day symptoms ( r = 0.24, p = 0.0006). The repeatability of the CSS in patients with no change in cough (n = 23) was high (intra-class correlation coefficient, 0.75; 95% confidence interval [CI], 0.51 to 0.88). Patients who reported an improvement in cough (n = 30) at follow-up visits had a significant improvement in the CSS (median, -2; 95% CI, -3 to -1; p = 0.0003)., Conclusions: The Korean version of the CSS correlated well with other tools for accessing cough severity in chronic cough patients. Therefore, it could be a reliable method for measuring chronic cough severity.

Purpose: There are no specific tools for measurement of the severity of chronic cough in Korea. We developed a Korean version of the Leicester Cough Questionnaire (LCQ) and tested its scaling and clinical properties., Methods: The LCQ was adapted for Korean conditions following a forward-backward translation procedure. All patients referred to chronic cough clinics at 5 university hospitals between May 2011 and October 2013 completed 2 questionnaires, the LCQ and the Short-Form 36 (SF-36), upon presentation and completed the LCQ and the Global Rating of Change (GRC) upon follow-up visits after 2 or 4 weeks. Concurrent validation, internal consistency, repeatability, and responsiveness were determined., Results: For the concurrent validation, the correlation coefficients (n=202 patients) between the LCQ and SF-36 varied between 0.42 and 0.58. The internal consistency of the LCQ (n=207) was high for each of the domains with a Cronbach's alpha coefficient of 0.82-0.94. The repeatability of the LCQ in patients with no change in cough (n=23) was high, with intra-class correlation coefficients of 0.66-0.81. Patients who reported an improvement in cough (n=30) on follow-up visits demonstrated significant improvement in each of the domains of the LCQ., Conclusions: The Korean version of the LCQ is a valid and reliable questionnaire for measurement of the severity of cough in patients with chronic cough.

Pyridoxalphosphate-6-azophenyl-2',4'-disulfonate (7a, PPADS), a nonselective P2X receptor antagonist, was extensively modified to develop more stable, potent, and selective P2X₃ receptor antagonists as potential antinociceptive agents. Based on the results of our previous report, all strong anionic groups in PPADS including phosphate and sulfonate groups were changed to carboxylic acids or deleted. The unstable azo (-NN-) linkage of 7a was transformed to more stable carbon-carbon, ether or amide linkages through the synthesis of the 5-hydroxyl-pyridine moieties with substituents at 2 position via a Diels-Alder reaction. This resulted in the retention of antagonistic activity (IC50 = 400 ∼ 700 nM) at the hP2X₃ receptor in the two-electrode voltage clamp (TEVC) assay system on the Xenopus oocytes. Introduction of bulky aromatic groups at the carbon linker, as in compounds 13 h-n, dramatically improved the selectivity profiles of hP2X₃ when compared with mP2X₁ and hP2X₇ receptors. Among the substituents tested at the 2-position, the m-phenoxybenzyl group showed optimum selectivity and potency at the hP2X₃ receptor. In searching for effective substituents at the 4- and 3-positions, we found that compound 36j, with 4-carboxaldehyde, 3-propenoic acid and 2-(m-phenoxy)benzyl groups, was the most potent and selective hP2X₃ receptor antagonist with an IC50 of 60 nM at hP2X₃ and marginal antagonistic activities of 10 μM at mP2X₁ and hP2X₇. Furthermore, using an ex-vivo assay system, we found that compound 36j potently inhibited pain signaling in the rat dorsal horn with 20 μM 36j displaying 65% inhibition while 20 μM pregabalin, a clinically available drug, showed only 31% inhibition., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

We report the preparation of mesoporous titania thin films with the R$\bar 3$m pore structure derived from the Im$\bar 3$m self-assembled ordering of the titania species and an EO(106)PO(70)EO(106) triblock copolymer. The films were spin-cast and then aged at 18 degrees C at a relative humidity of 70 %, which led to the orientation of the Im$\bar 3$m structure with the [111] direction perpendicular to the substrates. The [111] body-diagonal channels became vertical channels upon calcination at 400 degrees C, thus leading to thin films with vertical channels. The pores are ordered over a large area of up to 1 mum(2). The titania films can be formed on various types of substrates. By using a titania film formed on a Pt-coated Si wafer as a template, we produced by an electrochemical-deposition technique arrays of gold nanowires, whose morphology suggests that most of the pores of the titania thin films are accessible. The pore structure of vertical channels is stable up to 600 degrees C, at which temperature the wall materials crystallize into anatase.