[Show abstract][Hide abstract] ABSTRACT: This study investigated cytotoxicity, particularly autophagy, in RAW264.7 cells exposed to graphene oxide (GO) and its derivatives (dodecylamine-GO (DA-GO), reduced GO (rGO), and sodium dodecyl sulfate-rGO (SDS-rGO)). Appearance of amine stretching bands, out-of-plane C-H stretching vibrations, and S=O stretching bands in infrared spectra indicated the formation of DA-GO, rGO, and SDS-rGO, respectively. Light microscopy and microculture tetrazolium assay showed that all the GO types exerted cytotoxic effects on RAW264.7 cells in a concentration-dependent manner. Higher concentrations of the GO types downregulated the expression of PU.1, a unique transcription factor in monocytes and macrophages, and decreased the conversion of LC3A/B-I to LC3A/B-II, suggesting that PU.1 was associated with autophagy in RAW264.7 cells. These results suggested that surface-functionalized GOs exerted cytotoxic effects in a concentration-dependent manner by changing the expression of critical genes and inducing autophagy in macrophages.
Preview · Article · Oct 2015 · Journal of Nanomaterials
[Show abstract][Hide abstract] ABSTRACT: Background:
Asthma in the elderly (aged ≥65 years old) is a significant concern with high morbidity, but the pathophysiology remains unclear particularly in late-onset asthma. Recent studies suggest staphylococcal enterotoxin IgE (SE-IgE) sensitization to be a risk factor for asthma in general populations; however, the associations have not been examined in late-onset elderly asthma.
We aimed to examine the associations of SE-IgE sensitization with late-onset asthma in the elderly, using a database of elderly asthma cohort study.
A total of 249 elderly asthma patients and 98 controls were analyzed. At baseline, patients were assessed for demographics, atopy, induced sputum profiles, and comorbidities including chronic rhinosinusitis (CRS). Serum total IgE and SE-IgE levels were measured. Asthma severity was assessed on the basis of asthma outcomes during a 12-month follow-up period.
At baseline, serum SE-IgE concentrations were significantly higher in asthma patients than controls (median 0.16 [IQR 0.04-0.53] vs. 0.10 [0.01-0.19], p<0.001). Elderly asthma patients with high SE-IgE levels had specific characteristics of having more severe asthma, sputum eosinophilia and CRS, compared to those with lower SE-IgE levels. In multivariate logistic regression analyses, the associations between serum SE-IgE concentrations and severe asthma were significant, independently of co-variables (SE-IgE-high [≥0.35 kU/L] vs. negative [<0.10 kU/L] group: OR 7.47, 95% CI 1.86-30.03, p=0.005). Multiple correspondence analyses also showed that high serum SE-IgE level had close relationships with severe asthma, CRS and sputum eosinophilia together.
Conclusion and clinical relevance:
This is the first report on the significant associations of SE-IgE sensitization with late-onset asthma in the elderly, particularly severe eosinophilic asthma with CRS comorbidity. Our findings indicate a potential implication of SE in the high morbidity burden of elderly asthma, and suggest clues to the pathogenesis of severe late-onset eosinophilic asthma in the elderly. This article is protected by copyright. All rights reserved.
No preview · Article · Oct 2015 · Clinical & Experimental Allergy
[Show abstract][Hide abstract] ABSTRACT: Varenicline, a selective partial agonist/antagonist of the α4β2 nicotinic receptor, has proven effectiveness for smoking cessation by several randomized, controlled trials. Because few studies have evaluated the long-term efficacy of varenicline, we tried to evaluate the smoking status of varenicline users up to 3 years after the initial prescription of the drug.
We interviewed varenicline users who were prescribed the drug from June 2007 to May 2010 by telephone, from June 2010 to May 2011.
One-hundred and thirty-three of 250 varenicline users (53.2%) were available for the survey. Seven-day continuous abstinence from smoking was adhered to by 17 of 39 respondents (43.6%) at 1 year, and 11 of 36 (30.6%) and 19 of 58 (32.8%) at 2 and 3 years since the first use of varenicline, respectively. Compared to current smokers, successful quitters were older (55.0 years vs. 49.9 years, p=0.01), had better compliance to the 12-week course (27.7 vs. 9.3%, p=0.01), and had taken varenicline longer (10.1 vs. 5.9 weeks, p=0.01). Fifty-four of 71 current smokers (76.1%) were willing to stop smoking in the near future. The preferred ways to cease smoking were will-power (48.1%), varenicline (25.9%), nicotine replacement therapy (11.1%), and others (14.9%).
Smokers should be encouraged to stick to the proven way for recommended period of time for successful cessation of smoking.
[Show abstract][Hide abstract] ABSTRACT: Background
Though insurance claims data are useful for researching asthma, they have important limitations, such as a diagnostic inaccuracy and a lack of clinical information. To overcome these drawbacks, we used the novel method by merging the clinical data from our asthma cohort with the National Health Insurance (NHI) claims data.
Methods and Results
Longitudinal analysis of asthma-related healthcare use from the NHI claims database, merged with data of 736 patients registered in a Korean asthma cohort, was conducted for three consecutive years from registration of the cohort. Asthma-related asthma healthcare referred to outpatient and emergency department visits, hospitalizations, and the use of systemic corticosteroids. Univariate and multivariate logistic regression analysis was used to evaluate risk factors for asthma-related healthcare. Over three years after enrollment, many patients changed from tertiary to primary/secondary hospitals with a lack of maintenance of inhaled corticosteroid-based controllers. An independent risk factor for emergency visits was a previous history of asthma exacerbation. In hospitalizations, old age and Asthma Control Test (ACT) score variability were independent risk factors. An independent risk factor for per person cumulative duration of systemic corticosteroids was the FEV1 (Forced expiratory volume in one second)%. The use of systemic corticosteroids was independently associated with being female, the FEV1%, and ACT score variability.
We found that old age, being female, long-standing asthma, a low FEV1%, asthma brittleness, asthma drug compliance, and a history of asthma exacerbation were independent risk factors for increased asthma-related healthcare use in Korea.
[Show abstract][Hide abstract] ABSTRACT: Although South Korea received Bacillus Calmette-Guerin (BCG) vaccination which influence the result of tuberculin skin test (TST), only a few studies have described the usefulness of TST and interferon-γ releasing assay (IGRA) for the diagnosis of latent TB infection (LTBI). Therefore, we want to see the usefulness of TST and IGRA for the diagnosis of LTBI in household contacts investigation.Methods
We reviewed the 329 household contacts who visited Chung-Ang University Hospital from May 1, 2011 to February 28, 2014. To evaluate the effectiveness of TST and IGAR for the diagnosis of LTBI, we examined the concordance rate between the two tests according to the age and evaluated the risk factors for LTBI.ResultsThe concordance rate between the two tests in the 0-24 years, 25-54 years, and over 55 years old were 82.6% (kappa value =0.64, p<0.01), 68.9% (kappa value = 0.40, p<0.01) and 68.4% (kappa value=0.35, p<0.01), respectively. The ratio of positive TST and negative IGRA was higher between 25 and 44 years old, while the ratio of negative TST and positive IGRA was higher after 55 years old. The risk factor for LTBI was cavity (p<0.01) by using TST. When we use the IGRA, the risk factors are contact time (p=0.04) and age over 55 years old (p=0.02).Conclusion
The concordance rate between TST and IGRA was not good over 25 years old. And IGRA reflect the known risk factors more exactly.
[Show abstract][Hide abstract] ABSTRACT: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6β (ATF6B) is known to regulate ATFα-mediated ER stress response. The aim of this study is to investigate the associations of ATF6B genetic variants with aspirin-exacerbated respiratory disease (AERD) and its major phenotype, % decline of FEV1 by aspirin provocation.
Four common single nucleotide polymorphisms (SNPs) of ATF6B were genotyped and statistically analyzed in 93 AERD patients and 96 aspirin-tolerant asthma (ATA) as controls.
Logistic analysis revealed that 2 SNPs (rs2228628 and rs8111, P=0.008; corrected P=0.03) and 1 haplotype (ATF6B-ht4, P=0.005; corrected P=0.02) were significantly associated with % decline of FEV1 by aspirin provocation, whereas ATF6B polymorphisms and haplotypes were not associated with the risk of AERD.
Although further functional and replication studies are needed, our preliminary findings suggest that ATF6B may be related to obstructive phenotypes in response to aspirin exposure in adult asthmatics.
Full-text · Article · Mar 2014 · Allergy, asthma & immunology research
[Show abstract][Hide abstract] ABSTRACT: Background:
There has been no large-scale and comprehensive study of the differences between asthma in elderly asthmatics (EA) and non-elderly (i.e. young) asthmatics (NEA).
We performed principal component analysis (PCA) using 2067 asthmatics (434 EA and 1633 NEA) from the Korean Cohort for Reality and Evolution of adult Asthma (COREA). EA was defined as asthmatics with the chronological age of 65 or more and eleven clinical variables measured at enrollment were used for PCA; symptom score, symptom duration, number of exacerbation during previous one year, smoking pack year, number of controller medications, body mass index, predicted % of FEV1, predicted % FVC, post-bronchodilator FEV1/FVC ratio, atopy index and number of eosinophils in peripheral blood.
PCA of all asthmatics showed that EA and NEA were distinctly separated by the first and second principal component on the plot of individual asthmatics according to their scores. For further analysis, we divided all asthmatics into the EA and the NEA group and performed PCA again in each group. The first four principal components with eigenvalues ≥ 1.0 were identified in both groups and they explained 55.5% of the variance in the EA group and 52.4% in the NEA group respectively. Clinical variables showed distinctly different patterns of loading on the first four principal components between the EA and the NEA group.
EA and NEA have different compositional patterns underlying their clinical variables. These observations helped in understanding the differences between EA and NEA from the integrated view covering various clinical aspects.
No preview · Article · Oct 2013 · Respiratory Medicine
[Show abstract][Hide abstract] ABSTRACT: The therapeutic potential of human multipotent mesenchymal stromal cells, especially human adipose tissue-derived stem cells (hASC), is promising. However, there are concerns about the safety of infusion of hASC in human. Recently, we have experienced pulmonary embolism and infarct among family members who have taken multiple infusions of intravenous autologous hASC therapy. A 41-year-old man presented with chest pain for one month. Chest CT showed multiple pulmonary artery embolism and infarct at right lung. Serum D-dimer was 0.8 μg/mL (normal; 0-0.5 μg/mL). He had received intravenous autologous adipose tissue-derived stem cell therapy for cervical herniated intervertebral disc three times (one, two, and three months prior to the visit). His parents also received the same therapy five times and their chest CT also showed multiple pulmonary embolism. These cases represent artificial pulmonary embolisms and infarct after IV injection of hASC. Follow-up chest CT showed spontaneous resolution of lesions in all three patients.
Full-text · Article · Sep 2013 · Yonsei medical journal
[Show abstract][Hide abstract] ABSTRACT: Immunoglobulin E (IgE) is one of the central players in asthma and allergic diseases. Although the serum IgE level, a useful endophenotype, is generally increased in patients with asthma, genetic factors influencing IgE regulation in asthma are still not fully understood. To identify the genetic variations associated with total serum and mite-specific IgEs in asthmatics, a genome-wide association study (GWAS) of 657,366 single nucleotide polymorphisms (SNPs) was performed in 877 Korean asthmatics. This study found that several new genes might be associated with total IgE in asthmatics, such as CRIM1 (rs848512, P = 1.18×10(-6); rs711254, P = 6.73×10(-6)), ZNF71 (rs10404342, P = 7.60×10(-6)), TLN1 (rs4879926, P = 7.74×10(-6)), and SYNPO2 (rs1472066, P = 8.36×10(-6); rs1038770, P = 8.66×10(-6)). Regarding the association of specific IgE to house dust mites, it was observed that intergenic SNPs nearby to OPRK1 and LOC730217 might be associated with Dermatophagoides pteronyssinus (D.p.) and Dermatophagoides farinae (D.f.) in asthmatics, respectively. In further pathway analysis, the phosphatidylinositol signaling system and adherens junction pathways were estimated to play a role in the regulation of total IgE levels in asthma. Although functional evaluations and replications of these results in other populations are needed, this GWAS of serum IgE in asthmatics could facilitate improved understanding of the role of the newly identified genetic variants in asthma and its related phenotypes.
[Show abstract][Hide abstract] ABSTRACT: Asthma is a global health problem which threatens approximately 300 million patients worldwide. Among them, up to 20 % of the asthma patients are classified as aspirin exacerbated respiratory disease (AERD). Interleukin-1 receptor associated kinase (IRAK2) is associated with necrosis factor kappa B (NF-кB) pathway via interleukin-1 (IL-1) signaling. NF-кB pathway is known to be involved in asthma development, and several interleukin and IRAK family members have also been reported to be associated with asthma or AERD. Since IRAK2 plays an important role in the asthma etiology, we hypothesized that the genetic variants of IRAK2 may be associated with AERD. This study genotyped a total of 25 common single nucleotide polymorphisms (SNPs) in 163 AERD cases and 429 aspirin-tolerant asthma (ATA) controls. As a result, no significant association was found between the genetic variants of IRAK2 and AERD (P > 0.05). In further regression analysis for the forced expiratory volume in 1 s (FEV1) decline, an important phenotype for diagnosing AERD, although one haplotype (BL1_ht3) showed a nominal association with FEV1 decline (P = 0.04), the significance disappeared after correction for multiple testing (P > 0.05). Despite limitations in our study and need for replications, our results suggest that the genetic variants of IRAK2 might not be associated with AERD and the obstructive symptoms in asthma.
[Show abstract][Hide abstract] ABSTRACT: A 69-year-old female patient visited the emergency room with fever (38.3℃) and dyspnea. She had been taking prednisolone (5 mg once per day) and methotrexate (2.5 mg once per week) for rheumatoid arthritis for 2 years. Chest computed tomography (CT) showed bilateral, multifocal ground glass opacity with interlobular septal thickening. Peripheral blood leukocyte count was 6,520/mm(3) (neutrophils, 77.4%; eosinophils, 12.1%). During the night, mechanical ventilation was initiated due to the development of severe hypoxemia. Bronchoalveolar lavage fluid showed a high proportion of eosinophils (49%). Her symptoms improved dramatically after commencement of intravenous methylprednisolone therapy. This is the first report of idiopathic acute eosinophilic pneumonia developing in a current user of systemic corticosteroids.
[Show abstract][Hide abstract] ABSTRACT: Background:
Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function. ACE is increased in the bronchoalveolar lavage fluid from patients with IPF, suggesting the role of ACE in the pathogenesis of IPF. We evaluated the role of single-nucleotide polymorphisms (SNPs) in the development risk of IPF.
Two-hundred twenty patients with IPF and 456 healthy subjects were included in this study. Eleven polymorphisms were selected among those reported previously. Genotype was performed by single base extension.
Although absolute LD (|D'|= 1 and r(2 )= 1) was not present, 11 SNPs showed tight LDs. The logistic analysis of the all of 11 SNPs on the ACE genes between patients with IPF and healthy subjects were found to be related with the risk of IPF in recessive type. However, in patients with IPF diagnosed by surgical lung biopsy, only two SNP of -5538T>C and +21288_insdel SNPs were related with the risk of IPF in co-dominant type, and there were no SNPs related with the risk of IPF in dominant type. In patients with IPF diagnosed by clinical criteria or surgical lung biopsy, four SNPs on promoter (-5538T>C, -5508A>C, -3927T>C, -115T>C), one on intron (+15276A>G), one on exon (+21181G>A), and one in three prime region (+21288_insdel) were related with the risk of IPF.
This study showed a newly discovered SNP of ACE associated with the risk of development of IPF. ACE -5538T>C and -5508A>C significantly associated with risk of IPF in Korea.
No preview · Article · May 2013 · Beiträge zur Klinik der Tuberkulose
[Show abstract][Hide abstract] ABSTRACT: Background:
In this study, the association of asthma with CD53, a member of the tetraspanin family, was assessed for the first time in a mechanism-based study.
Genetic polymorphisms of CD53 were analyzed in 591 subjects and confirmed in a replication study of 1001 subjects. CD53 mRNA and protein levels were measured in peripheral blood leukocytes, and the effects of the promoter polymorphisms on nuclear factor binding were examined by electrophoretic mobility shift assay. Cellular functional studies were conducted by siRNA transfections.
Among tagging SNPs of CD53, the -1560 C>T in the promoter region was significantly associated with asthma risk. Compared with the CC genotype, the CT and TT genotypes were associated with a higher asthma risk, with odd ratios of 1.74 (P=0.009) and 2.03 (P=0.004), respectively. These findings were confirmed in the replication study with odd ratios of 1.355 (P=0.047) and 1.495 (P=0.039), respectively. The -1560 C>T promoter SNP had functional effects on nuclear protein binding as well as mRNA and protein expression levels in peripheral blood leukocytes. When CD53 was knocked down by siRNA in THP-1 human monocytic cells stimulated with house dust mite, the production of inflammatory cytokines as well as NFκB activity was significantly over-activated, suggesting that CD53 suppresses over-activation of inflammatory responses.
The -1560 C>T SNP is a functional promoter polymorphism that is significantly associated with population asthma risk, and is thought to act by directly modulating nuclear protein binding, thereby altering the expression of CD53, a suppressor of inflammatory cytokine production.
Full-text · Article · Jan 2013 · Biochimica et Biophysica Acta
[Show abstract][Hide abstract] ABSTRACT: Aspirin exacerbated respiratory disease (AERD) results in a severe asthma attack after aspirin ingestion in asthmatics. The filamin A interacting protein 1 (FILIP1) may play a crucial role in AERD pathogenesis by mediating T cell activation and membrane rearrangement. We investigated the association of FILIP1 variations with AERD and the fall rate of forced expiratory volume in one second (FEV1).
A total of 34 common FILIP1 single nucleotide polymorphisms (SNPs) were genotyped in 592 Korean asthmatic subjects that included 163 AERD patients and 429 aspirin-tolerant asthma (ATA) controls.
This study found that 5 SNPs (P=0.006-0.01) and 2 haplotypes (P=0.01-0.03) of FILIP1 showed nominal signals; however, corrections for the multiple testing revealed no significant associations with the development of AERD (P(corr)>0.05). In addition, association analysis of the genetic variants with the fall rate of FEV1, an important diagnostic marker of AERD, revealed no significant evidence (P(corr)>0.05).
Although further replications and functional evaluations are needed, our preliminary findings suggest that genetic variants of FILIP1 might be not associated with the onset of AERD.
Full-text · Article · Jan 2013 · Allergy, asthma & immunology research