Acute exacerbation of COPD increases the risk of hip fractures: a nested case-control study from the Korea National Health Insurance Service

Background/Aims@#Hip fracture and acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) could increase mortality in patients with COPD. There are no data on the relationship between AE-COPD and hip fracture, which may significantly affect the prognosis of patients with COPD. Therefore, we conducted this study to determine the effects of AE-COPD on hip fractures in patients with COPD. @*Methods@#This retrospective, nested, case-control study included 253,471 patients with COPD (≥ 40 years of age) identified from the Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) from 2002 to 2015. Among 176,598 patients with COPD, 1,415 patients with hip fractures were identified. Each case was matched to one control for age (within 10 years), sex, and year of COPD diagnosis. We estimated the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for hip fractures associated with AE-COPD using conditional logistic regression analysis, adjusting for underlying diseases and smoking history. @*Results@#In patients with AE-COPD, the risk of hip fracture was 2.50 times higher, regardless of systemic corticosteroid use and underlying disease (aOR, 2.50; 95% CI, 1.67 to 3.75). The risk of hip fracture increased if there was one episode of AE in the year before hip fractures (aOR, 2.25; 95% CI, 1.66 to 3.05). Moreover, the risk of hip fracture also increased in patients with more than two episodes of AE the year before hip fractures (aOR, 2.57; 95% CI, 1.61 to 4.10). @*Conclusions@#AE-COPD increases the risk of hip fracture regardless of underlying diseases, including osteoporosis, and treatment with systemic corticosteroids.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Effect of omalizumab as add-on therapy to Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) in Korean patients with severe persistent allergic asthma

Background/Aims@#Omalizumab is the first biologic known to be effective in patients with severe allergic asthma. @*Methods@#This study was conducted as a multicenter, single-group, open trial to evaluate the improvement in the quality of life with the additional administration of omalizumab for 24 weeks in Korean patients with severe persistent allergic asthma. @*Results@#Of the 44 patients, 31.8% were men and the mean age was 49.8 ± 11.8 years. A score improvement of 0.5 points or more in the Quality of Life Questionnaire for Korean Asthmatics (KAQLQ) was noted in 50.0% (22/44) of the patinets. In the improved group, the baseline total immunoglobulin E (IgE) level and the amount of omalizumab used were higher, and the day and night asthma symptoms were more severe, compared to those in the non-improved group. According to the Global Evaluation of Treatment Effectiveness, favorable outcomes were found in 78.6% of patients. The Korean asthma control test (p < 0.005) and forced expiratory volume in 1 second % predicted (FEV1%; p < 0.01) improved significantly in patients who received omalizumab treatment, compared to that at week 0, and the total dose of rescue systemic corticosteroids significantly decreased (p < 0.05). The improved group on KAQLQ showed a significant improvement in FEV1% (p < 0.001). @*Conclusions@#Omalizumab can be considered a biological treatment for Korean patients with severe allergic asthma. It is recommended to consider omalizumab as add-on therapy in patients with high baseline total IgE levels and severe asthma symptoms.

Peripheral Eosinophilia and Clinico-radiological Characteristics among Health Screening Program Recipients / 결핵및호흡기질환

BACKGROUND: Eosinophilia is well recognized in specific conditions. The objective of the present study was to determine clinico-radiologic characteristics of eosinophilia and changes in prevalence over 10 years in recipients of private health screening program at a tertiary hospital in Korea. METHODS: Data of private health screening program recipients at the health promotion center of Chung-Ang University Hospital from 2004 to 2013 were collected. Health-related questionnaires and laboratory findings of private health screening program with possible relation with eosinophilia were reviewed. Results of enzyme-linked immunosorbent assay (ELISA) for parasite, chest computed tomography, and pulmonary function test were also reviewed. RESULTS: The cumulative prevalence of eosinophilia was 4.0% (1,963 of 48,928). Prevalence of eosinophilia showed a decreased trend from 2004 to 2013. Most cases (96.6%) had mild degree of eosinophilia. Eosinophilic subjects were older and male-predominant. They showed lower levels of forced expiratory volume in 1 second (FEV₁%), forced vital capacity (FVC%), and FEV₁/FVC than those without eosinophilia. Eosinophilic subjects showed higher positive rate for common parasite in ELISA than those without eosinophilia. On radiologic findings, consolidation and ground glass opacities were positively associated with the degree of eosinophilia. When eosinophil was classified based on severity, statistically significant correlation between the severity of eosinophil and radiologic abnormalities was found. CONCLUSION: Eosinophilia is uncommon in healthy population. It usually occurs at a mild degree. Eosinophilic patients have more radiologic abnormalities compared to those without eosinophilia. Such radiologic abnormalities are associated with the severity of eosinophilia.

Genetic markers of severe cutaneous adverse reactions

Adverse drug reactions can cause considerable discomfort. They can be life-threatening in severe cases, requiring or prolonging hospitalization, impeding proper treatment, and increasing treatment costs considerably. Although the incidence of severe cutaneous adverse reactions (SCARs) is low, they can be serious, have permanent sequelae, or lead to death. A recent pharmacogenomic study confirmed that genetic factors can predispose an individual to SCARs. Genetic markers enable not only elucidation of the pathogenesis of SCARs, but also screening of susceptible subjects. The human leukocyte antigen (HLA) genotypes associated with SCARs include HLA-B*57:01 for abacavir (Caucasians), HLA-B*58:01 for allopurinol (Asians), HLA-B*15:02 (Han Chinese) and HLA-A*31:01 (Europeans and Koreans) for carbamazepine, HLA-B*59:01 for methazolamide (Koreans and Japanese), and HLA-B*13:01 for dapsone (Asians). Therefore, prescreening genetic testing could prevent severe drug hypersensitivity reactions. Large-scale epidemiologic studies are required to demonstrate the usefulness and cost-effectiveness of screening tests because their efficacy is affected by the genetic differences among ethnicities.

Epidemiological trend of pulmonary thromboembolism at a tertiary hospital in Korea

BACKGROUND/AIMS: Despite increasing interest in pulmonary thromboembolism (PTE), data on recent trends in PTE incidence are limited. This study evaluated the recent incidence rate of PTE. METHODS: We performed a retrospective chart review of patients with PTE admitted to Chung-Ang University Hospital during the 10-year period from 2006 to 2015. Age-standardized incidence and mortality rates were calculated by the direct method per 100,000 populations. To analyze the trend of risk factor, we also calculated the proportions of cancer, major operation, and recent major fracture over that time. RESULTS: Total crude incidence rate of PTE per 100,000 was 229.36 and the age-sex adjusted standardized incidence rate was 151.28 (95% confidence interval [CI], 127.88 to 177.10). The incidence rate have been significantly increased 1.083 times annually from 2006 (105.96 per 100,000) to 2015 (320.02 per 100,000) (95% CI, 1.049 to 1.118; p < 0.001). These incidences also increased annually in age group of 35 to 54, 55 to 74, and ≥ 75 years, and in both males (odds ratio [OR], 1.071; 95% CI, 1.019 to 1.127; p = 0.007) and females (OR, 1.091; 95% CI, 1.047 to 1.136; p < 0.001). Cancer accounted for most of the increase from 20.0% at 2006 to 2007 to 42.8% at 2014 to 2015 (OR, 1.154; 95% CI, 1.074 to 1.240; p < 0.001), while the proportions of recent fracture and major operation remained constant. CONCLUSIONS: The incidence of pulmonary embolism has gradually increased over the 10 years. The increase of PTE incidence was mainly due to increased proportion of cancer patients.

Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis

PURPOSE: Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. METHODS: A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. RESULTS: Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. CONCLUSIONS: Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two.

Serum micronutrients levels and clinical features of elderly asthmatics

PURPOSE: The prevalence of asthma in the elderly is rapidly increasing. However, we do not fully understand the pathogenesis of elderly asthma, especially for the roles of micronutrients. This study aimed to evaluate the associations between serum levels of micronutrients, including several vitamins and minerals, and clinical features of the elderly asthmatics. METHODS: A total of 317 asthmatics aged 65 or older were enrolled. Serum levels of vitamin D, vitamin B₁₂, folate, Mg, and Se were measured and then the associations between serum micronutrient levels and clinical features of elderly asthmatics were evaluated. RESULTS: Positive correlations with significance among serum levels of vitamin B₁₂, vitamin D, and folate were found. Serum micronutrients levels showed no difference according to the atopic status and symptom severity. The serum folate level was significantly associated with forced expiratory volume in 1 second, and serum vitamin B₁₂ and folate levels were significantly associated with serum total IgE level. Interestingly, elderly asthmatics with exacerbation history showed significantly lower serum levels of vitamin D and Mg, but significantly higher serum levels of Se. CONCLUSION: Serum levels of micronutrients, such as vitamin D, vitamin B₁₂, Mg, folate, and Se, were significantly associated with some clinical features of elderly asthmatics. Clinical meanings of these associations need to be investigated further.

Costs Attributable to Overweight and Obesity in Working Asthma Patients in the United States

PURPOSE: To estimate annual health care and productivity loss costs attributable to overweight or obesity in working asthmatic patients. MATERIALS AND METHODS: This study was conducted using the 2003–2013 Medical Expenditure Panel Survey (MEPS) in the United States. Patients aged 18 to 64 years with asthma were identified via self-reported diagnosis, a Clinical Classification Code of 128, or a ICD-9-CM code of 493.xx. All-cause health care costs were estimated using a generalized linear model with a log function and a gamma distribution. Productivity loss costs were estimated in relation to hourly wages and missed work days, and a two-part model was used to adjust for patients with zero costs. To estimate the costs attributable to overweight or obesity in asthma patients, costs were estimated by the recycled prediction method. RESULTS: Among 11670 working patients with a diagnosis of asthma, 4428 (35.2%) were obese and 3761 (33.0%) were overweight. The health care costs attributable to obesity and overweight in working asthma patients were estimated to be $878 [95% confidence interval (CI): $861–$895] and $257 (95% CI: $251–$262) per person per year, respectively, from 2003 to 2013. The productivity loss costs attributable to obesity and overweight among working asthma patients were $256 (95% CI: $253–$260) and $26 (95% CI: $26–$27) per person per year, respectively. CONCLUSION: Health care and productivity loss costs attributable to overweight and obesity in asthma patients are substantial. This study's results highlight the importance of effective public health and educational initiatives targeted at reducing overweight and obesity among patients with asthma, which may help lower the economic burden of asthma.

Bronchial Artery Aneurysm Presenting Hemoptysis, Initially Mis-diagnosed as Bronchial Arterio-venous Malformation: A Case Report

Normal bronchial arteries are small vessels that arise mostly from the descending thoracic aorta. Bronchial artery aneurysm is defined as a dilatation of the bronchial arteries with a diameter over 2 mm, and is reported in less than 1% of bronchial arterial angiography. A 70-year-old male patient was presented with hemoptysis. He had been treated for pulmonary tuberculosis 50 years ago. He also had a history of admission with hemoptysis 10 years ago, for which he was diagnosed as bronchiectasis on computed tomography imaging. Upon arrival to our hospital, abnormal vascular structure was detected on the mediastinum, arising from the descending thoracic aorta. It was dilated to 14 mm with a saccular form. Initially, we evaluated the structure as a bronchial arteriovenous malformation because it seemed to be drained into the pulmonary vein directly. For further evaluation, he had received a trans-catheter bronchial artery angiography. Both bronchial arteries were hypertrophied, but direct arteriovenous shunt was not detected; as such, we concluded this structure to be bronchial artery aneurysm. We performed embolization for both bronchial arteries and filled the aneurysm with coiling. He had no recurrence of hemoptysis and was discharged on 4 days post embolization. Our case reports an incidental bronchial artery aneurysm, which was initially misdiagnosed as bronchial arteriovenous anomaly, and finally treated with embolization and coiling.

Lung Microbiome Analysis in Steroid-Naїve Asthma Patients by Using Whole Sputum / 결핵및호흡기질환

BACKGROUND: Although recent metagenomic approaches have characterized the distinguished microbial compositions in airways of asthmatics, these results did not reach a consensus due to the small sample size, non-standardization of specimens and medication status. We conducted a metagenomics approach by using terminal restriction fragment length polymorphism (T-RFLP) analysis of the induced whole sputum representing both the cellular and fluid phases in a relative large number of steroid naïve asthmatics. METHODS: Induced whole sputum samples obtained from 36 healthy subjects and 89 steroid-naїve asthma patients were analyzed through T-RFLP analysis. RESULTS: In contrast to previous reports about microbiota in the asthmatic airways, the diversity of microbial composition was not significantly different between the controls and asthma patients (p=0.937). In an analysis of similarities, the global R-value showed a statistically significant difference but a very low separation (0.148, p=0.002). The dissimilarity in the bacterial communities between groups was 28.74%, and operational taxonomic units (OTUs) contributing to this difference were as follows: OTU 789 (Lachnospiraceae), 517 (Comamonadaceae, Acetobacteraceae , and Chloroplast), 633 (Prevotella), 645 (Actinobacteria and Propionibacterium acnes), 607 (Lactobacillus buchneri, Lactobacillus otakiensis, Lactobacillus sunkii, and Rhodobacteraceae), and 661 (Acinetobacter, Pseudomonas, and Leptotrichiaceae), and they were significantly more prevalent in the sputum of asthma patients than in the sputum of the controls. CONCLUSION: Before starting anti-asthmatic treatment, the microbiota in the whole sputum of patients with asthma showed a marginal difference from the microbiota in the whole sputum of the controls.

Intravenous immunoglobulin therapy in a selective IgG3 deficient patient with recurrent respiratory infections and asthma attacks

The IgG subclass deficiency is defined as a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal. IgG subclass deficiency can predispose to recurrent sinopulmonary infections. A 29-year-old female patient with a 4-year history of bronchial asthma presented with cough, sputum, dyspnea, and recurrent respiratory infections. She had frequently been treated with antibiotics and systemic steroids for recurrent respiratory infections and acute asthma exacerbations. Chest X-ray and computed tomography showed pectus excavatum and bronchial wall thickening without lung parenchymal abnormalities. On immunological evaluation, she was found to have a low serum IgG3, with normal total IgG concentration. Under diagnosis of selective IgG3 deficiency, she was started on monthly infusions of intravenous immunoglobulin (IVIG) therapy. The frequency and severity of respiratory infections and acute asthma exacerbations were markedly decreased during 3 years of IVIG therapy. Our case report suggests that a patient who has underlying selective IgG3 deficiency and asthma may benefit from IVIG therapy as this can significantly reduce the incidence and severity of recurrent respiratory infections and acute asthma exacerbations.

Epidemiology of chronic thromboembolic pulmonary hypertension in Korea: results from the Korean registry

BACKGROUND/AIMS: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is difficult for numerous reasons and is related with a poor prognosis. In Korea, the incidence of CTEPH and its clinical features are unknown. Thus, in this study, we evaluated the clinical characteristics and outcomes of CTEPH in a Korean cohort. METHODS: This study included South Korean patients diagnosed with CTEPH between September 2008 and October 2011. Baseline characteristics, treatments and outcomes were analyzed. RESULTS: A total of 134 patients were included in this study with 76 females (56.7%). Their median age was 58.3 +/- 15.9 years and dyspnea (112 patients, 83.5%) was the most common presenting symptom. Sixty-three patients (47%) had a history of acute pulmonary embolism or deep vein thrombosis, and six (4.5%) had pulmonary tuberculosis. In total, 28 patients (21%) underwent pulmonary thromboendarterectomy (PTE), and 99 patients had medical therapy. During the study period, 18 patients (13.4%) died. In a multivariate analysis, higher hemoglobin (relative risk [RR], 1.516; 95% confidence interval [CI], 1.053 to 2.184; p = 0.025) and lower total cholesterol levels (RR, 0.982; 95% CI, 0.965 to 0.999; p = 0.037) were associated with increased mortality. CONCLUSIONS: This was the first national cohort study of Korean patients with CTEPH. Accurate diagnosis, characterization and distributions of CTEPH are imperative for prompt treatment in patients, particularly those undergoing PTE.

Delayed diagnosis of allergic bronchopulmonary aspergillosis due to absence of asthmatic symptoms

Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease with small prevalence. Exposure to aspergillus mold causes immunologic hypersensitivity and may cause ranges of symptoms from minimal to detrimental outcomes. Diagnosing and treating the disease before the development of bronchiectasis may save the patient from poor outcomes. This report presents a case of recurrent ABPA without any symptom of asthma, which impeded the correct diagnosis even after numerous hospitalizations.

Seven-Day Continuous Abstinence Rate from Smoking at 1, 2, or 3 Years after the Use of Varenicline / 결핵및호흡기질환

BACKGROUND: Varenicline, a selective partial agonist/antagonist of the alpha4beta2 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. METHODS: We interviewed varenicline users who were prescribed the drug from June 2007 to May 2010 by telephone, from June 2010 to May 2011. RESULTS: 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%). CONCLUSION: Smokers should be encouraged to stick to the proven way for recommended period of time for successful cessation of smoking.

Two Cases of Newly Diagnosed Asthma with Spontaneous Pneumomediastinum During Asthma Exacerbation

Pneumomediastinum, a condition in which air is present in the mediastinum, is generally regarded as a benign, self-limited process. Rare life-threatening causes such as esophageal rupture must be excluded. A 26-year-old woman with allergic rhinitis presented with a 3-day history of increasing dyspnea, wheezing, and chest pain. Her high resolution CT (HRCT) showed extensive pneumomediastinum and subcutaneous emphysema without visible airway injury on the CT scan. With application of oxygen through a nasal cannula, bronchodilator inhalation, and systemic steroids, her pneumomediastinum and asthma symptoms were improved. A 30-year-old man with acute exacerbation of newly diagnosed asthma and spontaneous pneumomediastinum was treated with application of oxygen and asthma medication. Here, we reported two cases of newly diagnosed asthma with spontaneous pneumomediastinum during asthma exacerbation.

Polymorphisms of ATF6B Are Potentially Associated With FEV1 Decline by Aspirin Provocation in Asthmatics

PURPOSE: Endoplasmic reticulum (ER) stress has recently been observed to activate NF-kappaB and induce inflammatory responses such as asthma. Activating transcription factor 6beta (ATF6B) is known to regulate ATFalpha-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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Acute Eosinophilic Pneumonia Leading to Acute Respiratory Failure in a Current Systemic Corticosteroid User

A 69-year-old female patient visited the emergency room with fever (38.3degrees C) 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/mm3 (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.

A Case of Giant, Benign Schwannoma Associated with Total Lung Collapse by Bloody Effusion / 결핵및호흡기질환

Benign schwannoma is the most common neurogenic tumor in the mediastinum. Mediastinal benign schwannomas are most often asymptomatic and rarely accompanied by bloody pleural effusion. In the clinical analysis of 7 cases of pulmonary schwannomas, pleural effusion, and blood invasion were evident in 3 patients with malignant schwannoma. Herein, we report a rare case of giant, benign schwannoma presented with total collapse of right lung by massive, bloody pleural effusion.

Association Analysis Between FILIP1 Polymorphisms and Aspirin Hypersensitivity in Korean Asthmatics

PURPOSE: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.