Differential effects of sex on tuberculosis location and severity across the lifespan.

Disparities exist between sexes regarding tuberculosis (TB) incidence, as well as disease severity and outcome. Using a nationwide TB registry database, we explored the impact of sex and age on extrapulmonary TB (EPTB) among all enrolled patients by (1) calculating the female proportion for every age category according to TB-affected locations, (2) calculating the proportions of EPTB stratified by sex according to age, (3) conducting multivariable analysis to examine the impact of sex and age on EPTB likelihood, and (4) assessing the odds of EPTB for female compared to male as reference in every age category. Further, we explored the impact of sex and age on disease severity among pulmonary TB (PTB) patients. Of all the TB patients, 40.1% were female, with a male-to-female ratio of 1.49. The proportion of females was lowest in their fifties, resembling a U-shape. The male-to-female ratios in PTB and EPTB were 1.67 and 1.03, respectively. Compared to men, women were significantly associated with EPTB in their forties, fifties, and sixties. Female patients with PTB had significantly lower odds of having cavitation and positive smear test results in their fifties. Significant differences were found concerning TB location and severity between sexes, especially during reproductive age.

Prevalence of chronic rhinosinusitis and its relating factors in patients with bronchiectasis: findings from KMBARC registry.

BACKGROUND/AIMS: Patients with bronchiectasis often present with respiratory symptoms caused by chronic rhinosinusitis (CRS). However, studies on the prevalence of CRS and its relationship with bronchiectasis are limited. METHODS: The baseline characteristics of patients with bronchiectasis recruited from the Korean Multicenter Bronchiectasis Audit and Research Collaboration were analyzed. CRS diagnosis was determined by a physician, on the basis of medical records, upper airway symptoms, and/or radiologic abnormalities. Questionnaires for quality of life, fatigue, and depression were administered when patients were stable for a minimum of 4 weeks after the bronchiectasis exacerbation. RESULTS: The prevalence of CRS was 7.1% (66/931). Patients with CRS were significantly younger than those without CRS (60.5 ± 10.7 years vs. 64.6 ± 9.3 years, p = 0.001). Idiopathic bronchiectasis was more common in patients with CRS compared to those without CRS (53.0% vs. 36.0%, p = 0.006). Lung function, inflammatory markers, exacerbations, bronchiectasis severity, and scores for quality of life, fatigue, and depression did not differ between the two groups. In a logistic regression analysis, CRS was associated with age of bronchiectasis diagnosis (odds ratio [OR], 0.96; 95% confidence interval [CI], 0.94 to 0.99; p = 0.003) and idiopathic bronchiectasis (OR, 1.95; 95% CI, 1.12 to 3.34; p = 0.018). CONCLUSION: The prevalence of CRS was relatively low. CRS was not associated with the severity or clinical outcomes of bronchiectasis. Early diagnosis and idiopathic etiology were associated with CRS. Our findings reflect the low recognition of CRS in the clinical practice of bronchiectasis and highlight the need for awareness of CRS by adopting objective diagnostic criteria.

Respiratory Reviews in Asthma 2022.

Asthma is a chronic inflammatory disease of the airways characterized by varying and recurrent symptoms, reversible airway obstruction, and bronchospasm. In this paper, clinical important studies on asthma published between March 2021 and February 2022 were reviewed. A study on the relationship between asthma and chronic rhinosinusitis, bronchiectasis, and hormone replacement therapy was published. A journal on the usefulness of fractional exhaled nitric oxide for the prediction of severe acute exacerbation was also introduced. Studies on the effect of inhaler, one of the most important treatments for asthma, were published. Studies on the control of severe asthma continued. Phase 2 and 3 studies of new biologics were also published. As the coronavirus disease 2019 (COVID-19) pandemic has been prolonged, many studies have explored the prevalence and mortality of COVID-19 infection in asthma patients.

Bacterial etiology and pneumococcal urinary antigen in moderate exacerbation of chronic obstructive pulmonary disease.

Background: This study aimed to establish nationwide data for the distributions of typical and atypical bacterial pathogens in Korean patients with moderate acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and evaluate the clinical usefulness of a urinary antigen test (UAT) to detect Streptococcus pneumoniae. Methods: This study was a post hoc analysis of a randomized controlled trial designed to compare oral zabofloxacin with moxifloxacin for treating outpatients with moderate AECOPD. From clinics across South Korea, 342 subjects with AECOPD were enrolled, and their blood, sputum, and urine samples were collected at baseline. A serologic test, sputum culture and polymerase chain reaction (PCR), and UAT were performed to identify bacterial pathogens. Bacterial prevalence and regional distributions were analyzed. The patients' characteristics and clinical response between UAT-positive and UAT-negative groups were compared, as were the Streptococcus pneumoniae detection rates using conventional sputum culture and PCR versus UAT. Results: The most commonly isolated pathogen was Haemophilus influenzae (30.3%), followed by Streptococcus pneumoniae (24.7%) and Pseudomonas aeruginosa (14.0%), with no significant regional differences in bacterial distribution. Patients with positive UAT for Streptococcus pneumoniae showed no clinical failure when treated with respiratory quinolone (0.0%), whereas 11.8% of patients with negative UAT showed clinical failure (P=0.037). UAT showed moderate agreement with sputum culture by kappa coefficient (κ=0.476). Conclusions: The bacterial prevalence in patients with moderate AECOPD in South Korea showed correlations with the global prevalence, without significant regional differences. In outpatient settings, UAT has the potential to be used as a supplemental tool with sputum culture as a guide for determining the suspicion of bacterial exacerbation.

KMBARC registry: protocol for a multicentre observational cohort study on non-cystic fibrosis bronchiectasis in Korea.

INTRODUCTION: Despite the significant disease burden of bronchiectasis in Korea, no large-scale, representative prospective cohort studies have been conducted to evaluate the clinical characteristics of Korean patients with bronchiectasis, indicating an urgent need for cohort studies on bronchiectasis. METHODS AND ANALYSIS: The Korean Multicenter Bronchiectasis Audit and Research Collaboration (KMBARC) is a prospective, non-interventional observational cohort study on bronchiectasis in Korea. The inclusion criteria of this registry are as follows: (1) adult patients (aged ≥18 years) with or without respiratory symptoms (cough, chronic sputum and/or recurrent respiratory infection) and chest computed tomography revealing bronchiectasis affecting one or more lobes and (2) stable status at the time of registration: patients with bronchiectasis who were admitted for a respiratory aetiology can be enrolled at least 4 weeks after hospital discharge. The exclusion criteria are as follows: (1) bronchiectasis due to cystic fibrosis; (2) traction bronchiectasis associated with interstitial lung disease; (3) patients actively being treated for pneumonia, pulmonary tuberculosis or non-tuberculous mycobacterial infection; (4) patients who are unable or unwilling to provide informed consent; and (5) pregnant patients. Although the KMBARC questionnaires for baseline and annual follow-up data are similar to the European Multicentre Bronchiectasis Audit and Research Collaboration questionnaires, KMBARC has distinctive features such as use of Bronchiectasis Health Questionnaires, measurement with fatigue and depression scales, blood tests, use of consensus definition of exacerbations and information on emergency room or hospitalisation.We aim to recruit at least 1200 patients over the study period from more than 26 hospitals in South Korea. Patients will undergo a detailed baseline and yearly assessment for up to 5 years. The study objectives of the KMBARC registry are as follows: (1) uncovering the natural course of bronchiectasis; (2) aiding in establishing evidence-based bronchiectasis guidelines in Korea; and (3) encouraging and facilitating studies on bronchiectasis in Korea. ETHICS AND DISSEMINATION: This study received necessary approval from the Institutional Review Boards of all participating institutions. The Asan Medical Center Institutional Review Board gave overall approval for the study. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: KCT0003088.

Acute Exacerbation According to GOLD 2017 Categories in Patients with Chronic Obstructive Pulmonary Disease.

INTRODUCTION: The association between GOLD categorizations and future exacerbations has not been fully investigated. This study elucidates whether the GOLD 2017 classification is associated with different future exacerbation risk in patients with chronic obstructive pulmonary disease (COPD) compared with the previous GOLD categorization. Another objective was to investigate the impacts of the symptoms and FEV1 on the predicted future exacerbation independently of previous exacerbation history. METHODS: We analyzed patients from three prospective COPD cohorts (SNUH, KOCOSS, and KOLD) and evaluated the risk of moderate to severe exacerbation among different models, including GOLD grade (FEV1), GOLD 2011, and GOLD 2017. RESULTS: In total, 611 COPD patients were included (36 from SNUH, 257 from KOCOSS, and 318 from KOLD). GOLD 2017 classification, excluding FEV1% for categorization criteria, showed no differences in future exacerbation risk compared with GOLD grade and GOLD 2011 based on c-statistics. Among those with no frequent exacerbation history and FEV1 ≥50%, the group with more symptoms was significantly associated with future exacerbations than the group with less symptoms. A lower FEV1 (FEV1 <50%) was not associated with a higher future exacerbation risk than a higher FEV1 (FEV1 ≥50%), regardless of prior exacerbation history and symptom group. CONCLUSION: The GOLD 2017 classification was not different from GOLD grade and GOLD 2011 regarding the association with future exacerbation risk, and there were no significant differences in exacerbation risk according to FEV1%. This suggests that FEV1 might not be an important factor in future exacerbation risk. These results partly support the GOLD 2017 assessment tool.

Which GOLD B patients progress to GOLD D with the new classification?

BACKGROUND: The 2017 GOLD guidelines revised assessment of COPD by eliminating the FEV1 criterion. AIM: First, we explored the redistribution of 2011 GOLD groups by reference to the 2017 GOLD criteria. Second, we investigated the characteristics of GOLD B patients and the natural course of GOLD B patients according to the 2017 GOLD guidelines. METHODS: In total, 2,010 COPD patients in the Korean COPD Subgroup Study cohort were analyzed at baseline and 1 year after enrollment. RESULTS: The 2011 GOLD C patients were redistributed to the 2017 A (64.5%) and C (35.4%) groups. The 2011 GOLD D patients were redistributed to the 2017 B (61.6%) and D (38.6%) groups. The GOLD B patients constituted 62.7% of all patients according to the 2017 classification. Such patients exhibited higher % predicted FEV1 values, longer six-minute walk distances, fewer symptoms, and lower inflammatory marker levels than GOLD D patients. Most GOLD B patients remained in that group (69.1%), but 13.8% progressed to group D at 1-year follow-up. The factors associated with progression from GOLD B to GOLD D were older age, higher modified Medical Research Council (mMRC) and St George's Respiratory Questionnaire (SGRQ) symptom scores, and a lower % predicted FEV1 value. CONCLUSION: Severe symptoms, poorer health status, and greater airflow limitation increased patients' risk of exacerbation and progression from group B to group D when the 2017 GOLD criteria were applied.

Use of serology and polymerase chain reaction to detect atypical respiratory pathogens during acute exacerbation of chronic obstructive pulmonary disease.

BACKGROUND/AIMS: To use serological and multiplex polymerase chain reaction (PCR) assays to examine sputum samples from patients experiencing acute exacerbation of chronic obstructive pulmonary disease (AECOPD) for the presence of atypical pathogens, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila. METHODS: From September 2012 to February 2014, 341 patients with AECOPD attending outpatient clinics were enrolled as part of a randomized, double-blind, multicenter study. A commercial enzyme-linked immunosorbent assay was used to measure serum immunoglobulin M (IgM) and IgG antibody titers on the first day of the study and at 36 days post-enrollment. Multiplex PCR was used to test sputum samples for the presence of atypical pathogens. A urinary antigen test for L. pneumophila was performed on the first day. RESULTS: Nineteen patients (5.6%) showed serological evidence of acute infection with M. pneumoniae. Also, one and seven patients (2%) showed serological evidence of acute infection with C. pneumoniae and L. pneumophila, respectively. All DNA samples were negative for M. pneumoniae, C. pneumoniae, and L. pneumophila according to PCR. Only one urine sample was positive for L. pneumophila antigen, but serologic evidence was lacking. CONCLUSION: Serological testing suggested that infection by atypical pathogens during AECOPD was relatively uncommon. In addition, PCR provided no direct evidence of infection by atypical pathogens. Thus, atypical pathogens may not be a major cause of AECOPD in South Korea.

Effect of adipose tissue volume on prognosis in patients with non-small cell lung cancer.

OBJECTIVE: This study evaluated the relationship between adipose tissue volume and survival in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively included 171 NSCLC patients who underwent staging 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and subsequent curative surgical resection or definite chemoradiotherapy. Maximum standardized uptake value (SUV) of lung cancer normalized by lean body mass (SULmax) and volume and mean SUV of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were derived from PET/CT images. The relationships of volume and mean SUV of SAT and VAT with survival were assessed. RESULTS: Of the 171 patients, 79 (46.2%) experienced disease progression and 61 patients (35.7%) died during follow-up. SULmax had significant negative correlation with SAT volume (p = 0.003), but not with VAT volume and mean SUV of SAT and VAT (p > 0.05). On multivariate analysis, advanced TNM stage and high SULmax were significantly related with worse progression-free survival (PFS) and high SAT volume was significantly associated with better PFS (p < 0.05). Patient subgroups of high SULmax (>4.6) and low SAT volume (<75 cm3) had the highest disease progression rate of 61.7%, while other patient subgroups showed rates between 21.1 and 33.3%. SAT volume was significantly related with overall survival on univariate analysis, but failed to show significance on multivariate analysis. Only TNM stage was an independent prognostic factor for overall survival. CONCLUSION: SAT volume had significant favorable effect on PFS in patients with NSCLC.

Which bronchodilator reversibility criteria can predict severe acute exacerbation in chronic obstructive pulmonary disease patients?

BACKGROUND: It is unclear whether various bronchodilator reversibility (BDR) criteria affect the prognosis of chronic obstructive pulmonary disease (COPD). The aim of this study is to evaluate the impact of positive BDR defined according to various BDR criteria on the risk of severe acute exacerbation (AE) in COPD patients. METHODS: Patients from four prospective COPD cohorts in South Korea who underwent follow-up for at least 1 year were enrolled in this study. The assessed BDR criteria included the Global Initiative for Chronic Obstructive Lung Disease (GOLD), American Thoracic Society (ATS), American College of Chest Physicians, (ACCP), major criteria of the Spanish definition of asthma-COPD overlap syndrome (ACOS), criteria compatible with ACOS in the Global Initiative for Asthma (GINA), and European Respiratory Society (ERS). The rate of patients with severe AE who required hospitalization within 1 year due to BDR results according to each set of criteria was analyzed using logistic regression models. RESULTS: Among a total of 854 patients, the BDR-positive cases varied according to the criteria used. There was a 3.5% positive BDR rate according to GINA and a 29.9% rate according to the ATS criteria. Positive BDR according to the GOLD criteria was significantly associated with a decreased risk of severe AE (adjusted odds ratio (aOR) = 0.38; 95% Confidence interval (CI) = 0.15-0.93). This result remained statistically significant even in a sensitivity analysis that included only participants with a smoking history of at least 10 pack-years and in the analysis for the propensity score-matched participants. CONCLUSIONS: Among different criteria for positive BDR, the use of the GOLD ones was significantly associated with a decreased risk of severe AE in COPD patients. Increase use of ICS/LABA may have affected this relationship.

Prognostic Significance of FDG Uptake of Bone Marrow on PET/CT in Patients With Non-Small-Cell Lung Cancer After Curative Surgical Resection.

BACKGROUND: This study evaluated the relationship between 18F-fluorodeoxyglucose (FDG) uptake in bone marrow (BM) on positron emission tomography (PET)/computed tomography (CT) imaging and serum inflammatory markers and assessed the prognostic value of FDG uptake of BM in patients with non-small-cell lung cancer (NSCLC) who underwent curative surgical resection. PATIENTS AND METHODS: We retrospectively enrolled 110 NSCLC patients who underwent FDG PET/CT imaging and subsequent curative surgical resection. The maximum standardized uptake value of NSCLC (Tmax), mean FDG uptake of BM (BM SUV), and BM to liver uptake ratio (BLR) were measured. The relationships between BM SUV, BLR, and serum inflammatory markers were evaluated and the prognostic significance of PET/CT parameters for predicting recurrence-free survival (RFS) and overall survival (OS) were assessed. RESULTS: BM SUV and BLR were significantly associated with serum C-reactive protein (CRP) level, white blood cell count, and the neutrophil to lymphocyte ratio (NLR). BLR was also significantly correlated with serum albumin and the platelet to lymphocyte ratio. In univariate analysis, tumor, node, metastases (TNM) stage, serum CRP level, NLR, Tmax, and BLR were significant prognostic factors for RFS and OS, whereas histopathology and tumor size were significant prognostic factors for RFS. In multivariate analysis, BLR, histopathology, TNM stage, and Tmax were independent prognostic factors for RFS and TNM stage and Tmax were independent prognostic factors for OS. CONCLUSION: FDG uptake of BM on PET/CT imaging was correlated with serum inflammatory markers and was an independent predictor for RFS, along with FDG uptake of NSCLC.

Chronic bronchitis is an independently associated factor for more symptom and high-risk groups.

BACKGROUND: The chronic bronchitis (CB) phenotype has been associated with poor quality of life and an increased risk of disease in patients with COPD. However, little information exists regarding the relationship between the CB phenotype and the COPD assessment test (CAT) score. The goal of this study was to reveal the different pattern of CAT scores between CB and non-CB patients. Moreover, we aimed to investigate whether the CB phenotype is an independently associated factor for more symptom and high-risk groups. METHODS: Data were obtained from the Korea COPD Subgroup Study cohort recruited from 46 centers in South Korea since April 2012. CB patients were defined as having a chronic cough and sputum for 3 months per year, for a period of 2 consecutive years. We investigated the pattern of CAT and subquestionnaire scores between CB and non-CB patients. We also analyzed the proportion of CB phenotypes in each Global initiative for chronic Obstructive Lung Disease (GOLD) stage. Finally, we performed a logistic regression analysis to identify whether the CB phenotype was an independently associated factor for more symptom and high-risk groups. RESULTS: Of the 1,106 study patients, 11.5% of patients were found to have a CB phenotype. CB phenotypes were most common in GOLD III (GOLD 2006) and GOLD D (GOLD 2015) stages. CAT scores were significantly higher in CB patients not only in terms of the total score but also for each subquestionnaire. Logistic regression revealed that the CB phenotype is an independently associated factor for more symptom and high-risk groups. CONCLUSION: The present study revealed that CB patients have higher CAT scores and subquestionnaire results compared to non-CB patients. Additionally, we demonstrated that the CB phenotype is an independently associated factor for both more symptom and high-risk groups.

Indolent metastatic squamous cell carcinoma of unknown primary in the intrathoracic lymph node: a case report and review of the literatures.

Metastatic squamous cell carcinoma from a cancer of unknown primary (CUP) affecting the intrathoracic lymph node is very rare. We reported a case of metastatic squamous cell carcinoma in the hilar and interlobar lymph node from a patient with CUP and reviewed the associated literature. Abnormal mass in the right hilar area was incidentally detected. A chest computed tomography scan showed a 2.5-cm diameter mass in the right hilum that had changed little in size for 3 years. The patient underwent a right pneumonectomy and mediastinal lymph node dissection. A metastatic squamous cell carcinoma in the hilar and interlobar lymph nodes without a primary lung or other lesion was diagnosed. The patient received adjuvant chemotherapy for a diagnosis of T0N1M0 lung cancer.

Successful early rituximab treatment in a case of systemic lupus erythematosus with potentially fatal diffuse alveolar hemorrhage.

Diffuse alveolar hemorrhage (DAH) is a rare but devastating complication of systemic lupus erythematosus (SLE) with a high early mortality rate. DAH seldom occurs without active organ involvement. Recently, rituximab (RTX), a B cell-targeted therapy, has been reported to be effective for life-threatening autoimmune diseases. We describe a SLE patient who presented with acute respiratory failure due to DAH without other active organ involvement. This condition was dramatically improved with RTX without cyclophosphamide.

Risk factors influencing rebleeding after bronchial artery embolization on the management of hemoptysis associated with pulmonary tuberculosis.

BACKGROUND: Hemoptysis due to pulmonary tuberculosis (TB) frequently develops in Korea where the prevalence of TB is intermediate. The effect of bronchial artery embolization (BAE) on the control of massive hemoptysis has been well known. This study is designed to identify the risk factors contributing to rebleeding after BAE in patients with TB. METHODS: We retrospectively evaluated risk factors and the time for rebleeding after BAE in 72 patients presenting with hemoptysis. RESULTS: The overall immediate success rate of BAE was 93.1% (67 of 72 patients). Of the 29 patients (40.3%) who showed rebleeding after BAE, 13 patients experienced rebleeding within 1 month, and 14 patients between 1 month to 1 year. The existence of a shunt in angiographic finding, aspergilloma, and diabetes mellitus were risk factors of rebleeding after BAE in multivariate analysis. CONCLUSION: BAE was very effective for obtaining immediate bleeding control in hemoptysis associated with active TB or post-TB sequelae. It is important to observe whether or not rebleeding occurs up to 1 year of BAE especially in TB patients with aspergilloma, DM, or a shunt. Even rebleeding can be managed well by second BAE.

The effect of post-treatment N-acetylcysteine in LPS-induced acute lung injury of rats.

BACKGROUND: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. METHODS: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) were measured in BALF. Nuclear factor κB (NF-κB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. RESULTS: TNF-α and IL-1ß concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5±2.8 nmol/mL vs. 16.5±1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4±1.8 unit/g vs. 11.2±6.3 unit/g, tissue) (p<0.048). The concentration of NF-κB in NAC treatment group was significantly lower than that of LPS group (0.3±0.1 ng/µL vs. 0.4±0.2 ng/µL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. CONCLUSION: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-κB activation.

Remarkable Effect of Gefitinib Retreatment in a Lung Cancer Patient With Lepidic Predominat Adenocarcinoma who had Experienced Favorable Results From Initial Treatment With Gefitinib: A Case Report.

Gefitnib is an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, and it has a certain efficacy against non-small cell lung cancer. There are some reports that the non-small cell lung cancer patients who experienced disease progression after responding to gefitinib were again sensitive to re-administration of gefitinib following temporary cessation of gefitinib. This is the case report showing a remarkable effect of gefitinib re-treatment in a patient with metastatic invasive adenocarinoma who had experienced favorable results from the initial treatment with gefitinib.

Association of IKBA gene polymorphisms with the development of asthma.

Nuclear factor-κB (NF-κB) orchestrates the expression of genes responsible for airway inflammation and remodeling in asthma. The activity of NF-κB is tightly regulated by IKBA, which may be modulated by genetic polymorphisms of the IKBA gene. We investigated the association between asthma susceptibility and IKBA gene polymorphisms in a Korean population. Genotyping was performed in BA (bronchial asthma) and NC (normal control). We measured reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay, and luciferase reporter assays, respectively. A -673A>T (rs2233407) was associated with asthma development in subjects with atopic asthma (odds ratio = 0.56, p = 0.004). The IKBA mRNA level was higher in B-cell lines with the rs2233407 TT genotype compared with those with the AA genotype (p = 0.024). The luciferase activity of the rs2233407 T genotype was higher than that of the A (p = 0.002). The cytoplasmic levels of total IKBA and IKBA [p-S32] were higher in B cell lines of the rs2233407 TT genotype than those of the AA (p = 0.016 and p = 0.036, respectively), whereas nuclear NF-κB activity in cells with the IKBA rs2233407 AA genotype was higher than in cells with the AA (p = 0.038). The IKBA rs2233407 A>T polymorphism may predispose individuals to the development of atopic asthma via regulation of IKBA gene expression at the transcriptional level.

Association of IL-17RB gene polymorphism with asthma.

BACKGROUND: Interleukin (IL)-17E is a member of the IL-17 family, which induces IL-4, IL-5, IL-13, and eotaxin in experimental animals via IL-17 receptor B (IL-17RB). The activation of IL-17RB amplifies allergic-type inflammatory responses by inducing Jun kinase (or JNK), p38 mitogen-activated protein kinase (or MAPK), and nuclear factor-kappaB. OBJECTIVES: We examined the association of polymorphisms in the IL-17RB gene with asthma susceptibility and investigated the effects of those polymorphisms on the transcription of various IL-17RB isoforms. METHODS: In total, 954 asthmatic patients or 265 healthy control subjects were screened for polymorphisms in IL-17RB by single-base extension. The messenger RNA expression IL-17RB in B-cell lines derived from patients was also measured by reverse transcription-polymerase chain reaction. RESULTS: Direct sequencing of 24 unrelated Korean DNA samples revealed 18 genetic variants, including four insertion/deletions and 14 single-nucleotide polymorphisms (SNPs). Six of the SNPs (-1465G>A, +5661G>A, +6297T>C [Y123Y], +13797C>T, +18661C>T, and +18965G>A) were used to screen a larger group of subjects. Intronic polymorphism +5661G>A was significantly associated with the development of asthma (p = 0.001); moreover, a minor allele of IL-17RB +5661G>A appeared at a lower frequency in the asthmatic patients than in the healthy control subjects (0.13 vs 0.19, respectively). The IL-17RB messenger RNA expression in B cells homozygous for IL-17RB+ 5661GG was significantly higher than that in B cells homozygous for IL-17RB+5661AA (p = 0.002). CONCLUSIONS: A rare allele of IL-17RB +5661G>A may have a protective role against the development of asthma via regulation at the level of transcription. The SNPs identified in this study may be used to develop markers to assess the risk of asthma.