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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)., Conclusion: 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.

We estimated the exposure to ambient air pollutants and analyzed the associations with allergic diseases. We enrolled 177 children with atopic dermatitis (AD) and 70 asthmatic adults living in Seoul Metropolitan Area, Korea, and followed for 17months between August 2013 and December 2014. Parents or patients recorded symptom scores on a daily basis. Exposure to particulate matter with a diameter <10μm (PM 10 ) and nitrogen dioxide (NO 2 ) was estimated in four different ways in each individual, using the AQ1 (measurements from the nearest air quality monitoring station to residential houses), AQ2 (measurements modified from AQ1 with the indoor level of air pollutants and time activity of each individual), AQ1-DI, and AQ2-DI (measurements modified from AQ1 and AQ2, respectively, with daily inhalation intakes of air pollutants). A generalized linear mixed model (GLMM) was used to analyze the associations between exposure metrics and clinical symptoms after adjusting for ambient temperature and humidity, age, season, gender, and time trend. The exposure metrics for PM 10 and NO 2 showed different distributions. Symptoms of AD and asthma were positively associated with exposure to PM 10 , but not NO 2 , in all exposure metrics. The effect size of PM 10 exposure on asthma symptoms was slightly greater in metrics with inhalation capacity (AQ-DIs) than in those without (AQs). This pattern was not observed in AD. Exposure to PM 10 is associated with symptom aggravation in childhood AD and adult asthma. Different exposure estimates may be used to evaluate the impact of air pollution on different allergic diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Acute exacerbations are major drivers of COPD deterioration. However, limited data are available for the prevalence of severe exacerbations and impact of asthma on severe exacerbations, especially in patients with mild-to-moderate COPD., Methods: Patients with mild-to-moderate COPD (≥40 years) were extracted from Korean National Health and Nutrition Examination Survey data (2007-2012) and were linked to the national health insurance reimbursement database to obtain medical service utilization records., Results: Of the 2,397 patients with mild-to-moderate COPD, 111 (4.6%) had severe exacerbations over the 6 years (0.012/person-year). Severe exacerbations were more frequent in the COPD patients with concomitant self-reported physician-diagnosed asthma compared with only COPD patients (P<0.001). A multiple logistic regression presented that asthma was an independent risk factor of severe exacerbations in patients with mild-to-moderate COPD regardless of adjustment for all possible confounding factors (adjusted odds ratio, 1.67; 95% confidence interval, 1.002-2.77, P=0.049). In addition, age, female, poor lung function, use of inhalers, and low EuroQoL five dimensions questionnaire index values were independently associated with severe exacerbation in patients with mild-to-moderate COPD., Conclusion: In this population-based study, the prevalence of severe exacerbations in patients with mild-to-moderate COPD was relatively low, compared with previous clinical interventional studies. Coexisting asthma significantly impacted the frequency of severe exacerbations in patients with mild-to-moderate COPD, suggesting application of an exacerbation preventive strategy in these patients.

Background and Objective: Airway hyperresponsiveness is a common feature of asthma. Methacholine and mannitol are two representative agonists for bronchial challenge. They have theoretically different mechanisms of action, and may have different diagnostic properties. However, their difference has not been directly evaluated among Korean adults. In this study, we compare the diagnostic properties of methacholine and mannitol bronchial provocation tests., Methods: Asthmatic patients and non-asthmatic controls were recruited prospectively from four referral hospitals in Korea. Participants were challenged with each of methacholine and mannitol inhalation on different days. Their diagnostic utility was evaluated by calculating their sensitivity and specificity for asthma diagnosis. Response-dose ratio was also compared., Results: A total of 50 asthmatic adults and 54 controls were enrolled (mean age 43.8 years). The sensitivity and specificity of mannitol challenge (defined by a PD15 of <635 mg) were 48.0% and 92.6%, respectively, whereas those of methacholine (defined by a PC20 of <16 mg/mL) were 42.0% and 98.1%, respectively. Twenty asthmatic participants (24%) showed positive response to a single agonist only. In the receiver operating curve analyses using response-dose ratio values, area under the curve was 0.77 (95% confidence interval (CI): 0.68-0.86) for mannitol, and 0.89 (95% CI: 0.83-0.95) for methacholine. The correlations between log- transformed mannitol and methacholine response-dose ratios were significant but moderate (r = 0.683, P < 0.001)., Conclusions: The present study demonstrated overall similar diagnostic properties of two diagnostic tests, but also suggested their intercomplementary roles for asthma. The clinical trial registration number at ClinicalTrial.gov is NCT02104284., (© 2014 Asian Pacific Society of Respirology.)

Background: Nonasthmatic eosinophilic bronchitis (NAEB) and cough variant asthma (CVA) are common causes of chronic cough. Both are characterized by eosinophilic inflammation in the airways. However, airway hyperresponsiveness, which is a characteristic feature of CVA, is not observed in NAEB. We hypothesized that endogenous bronchodilator S-nitrosothiol (SNO) levels are different between patients with NAEB and CVA., Methods: SNO concentrations in sputum supernatant were measured using a commercially available kit in 20 NAEB and 21 CVA patients., Results: The mean sputum eosinophil counts and exhaled nitric oxide values were similar in patients with NAEB (12.4 ± 2.3%, 80.6 ± 8.1 ppb) and CVA (15.3 ± 3.7%, 97.7 ± 9.2 ppb). By contrast, SNO levels in the airway lining fluid of NAEB patients were substantially higher than those of CVA patients (87.1 ± 9.8 vs. 46.8 ± 4.8 μM; p < 0.05)., Conclusions: SNOs may be an important factor in determining the development of airway hyperresponsiveness in the presence of eosinophilic inflammation., (Copyright © 2011 S. Karger AG, Basel.)

Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensitized with OVA plus dsRNA. Lung infiltration of inflammatory cells, especially neutrophils, was increased by repeated challenge with OVA plus dsRNA, as compared to OVA alone. The neutrophilic inflammation enhanced by dsRNA was partly abolished in the absence of IFN-gamma or IL-17 gene expression, whereas unaffected in the absence of IL-13. In terms of the roles of NOSs, dsRNA-enhanced neutrophilic inflammation was significantly decreased in inducible NOS (iNOS)-deficient mice compared to wild type controls; in addition, this phenotype was inhibited by treatment with a non-specific NOS inhibitor (L-NAME) or an specific inhibitor (1400 W), but not with a specific endothelial NOS inhibitor (AP-CAV peptide). Taken together, these findings suggest that iNOS pathway is important in the development of virus-associated exacerbation of neutrophilic inflammation, which is dependent on both Th1 and Th17 cell responses.

Although CpG methylation is thought to be a negative regulator of gene transcription, its relationship with cytokine expression remains unclear. Interleukin (IL)-4 and interferon (IFN)-gamma are major cytokines that affect the differentiation of naïve CD4+ T lymphocytes into the Th1 and Th2 lineage. We used bisulfite deoxyribonucleic acid modification and sequencing to examine the relationship between CpG methylation and IL-4 and IFN-gamma gene expression before and after allergen stimulation in human CD4+ T lymphocytes from sensitized hosts. In naïve cells, the CpGs in the promoter regions were methylated largely in both the IL-4 and IFN-gamma genes. After Dermatophagoides pteronyssinus/Dermatophagoides farinae stimulation, the degree of unmethylation in the IL-4 gene increased in cells from patients with bronchial asthma. After phytohemagglutinin stimulation, the degree of unmethylation increased in cells from nonallergic control subjects. The concentration of IL-4 was strongly correlated with the degree of unmethylation in the patient group. These data suggest that CpGs located at -80 of the IL-4 gene and at -295, -186, and +122 of the IFN-gamma gene have regulatory activities important for cytokine expression. We conclude that the stimulation of CD4+ T lymphocytes causes considerable increases in the degree of unmethylation and that in sensitized hosts, the extent of unmethylation correlates with the concentration of IL-4.

Background: Although asthma is a common cause of morbidity in adults, relatively few objectively measured population studies of asthma prevalence in adult populations have been conducted., Objective: To evaluate the prevalence of asthma, based on both a questionnaire and methacholine bronchial provocation test, and to determine the risk factors of asthma prevalence in an adult population., Methods: A total of 2,467 adults, who were randomly selected from metropolitan urban, non-metropolitan urban and rural areas, responded to the modified ISAAC questionnaire, and underwent methacholine bronchial provocation tests and skin prick tests to locally common aeroallergens., Results: The prevalence of current asthma based on the questionnaire and the methacholine challenge was 2.0% in adults younger than 40, 3.8% in 40- to 54-year-olds, 7.7% in 55- to 64-year-olds and 12.7% in those aged 65 or higher. For subjects of 55-64 years, active smoking was found to be significantly related with the prevalence of current asthma and bronchial hyper-responsiveness, although smoking was positively associated with percentage predictive value of forced expiratory volume of 1 s (FEV1)., Conclusion: The prevalence of current asthma is common among the elderly, and active smoking may play an important role in the development of asthma and bronchial hyper-responsiveness among the elderly.

The pathogenetic mechanism of nonatopic asthma has not yet been defined. The idea of a possible involvement of autoimmunity in the pathogenesis of nonatopic asthma has been proposed by earlier studies. To evaluate the possible involvement of autoimmune response against bronchial epithelial cell in the pathogenesis of nonatopic asthma, we measured circulating autoantibodies to cultured human bronchial epithelial cell (BEAS-2B cell line) using enzyme-linked immunosorbent assay. We used stored serum samples form 38 age-matched healthy controls, 26 adult patients with atopic asthma, 16 adult patients with nonatopic asthma, and 12 adult patients with systemic lupus erythematosus. Levels of IgG autoantibodies to bronchial epithelial cell were significantly higher in patients with nonatopic asthma (mean+/-SD of absorbance values; 0.135+/-0.030) and systemic lupus erythematosus (0.293+/-0.181) than in healthy controls (0.112+/-0.016) and patients with atopic asthma (0.116+/-0.031) (p<0.05). This study showed that levels of circulating IgG autoantibodies to bronchial epithelial cell were increased in adult patients with nonatopic asthma. Further studies are needed to evaluate the possible involvement of autoimmune mechanism in the pathogenesis of nonatopic asthma.

There have been several reports on the effectiveness of endoscopic sinus surgery (ESS) in asthmatic patients with chronic rhinosinusitis. Whether ESS has a positive effect on the clinical course of asthma still remains controversial. There have been several subjective evaluations but few objective results. We performed a study to evaluate the effectiveness of ESS in 19 patients with asthma who underwent ESS for rhinosinusitis. The use of antiasthma medication and postoperative asthma symptoms was analyzed. Objective changes of pulmonary function tests were evaluated. There was a significant improvement in diurnal and nocturnal asthma symptoms. Improvements in asthma medication scores were also confirmed, and individual asthma symptoms (dyspnea, cough, wheezing, and sputum production) improved significantly. Despite a reduction in use of antiasthma medication after ESS, the parameters of the pulmonary function tests did not change. Both subjectively and objectively, it seems that ESS, when used to treat asthmatic patients with chronic rhinosinusitis, can play a significant role in the clinical improvement of asthma.

Background: Although there have been a few reports of occupational asthma due to cellulase in several occupational settings, this is the first case of cellulase-induced occupational asthma in an employee working in the textile industry. Its pathogenetic mechanism remains to be further clarified., Objective: It is important to alert physicians to the possibility of occupational asthma caused by cellulase in workers of the textile industry., Methods and Results: The patient had atopy and strong positive responses to cellulase extract on skin prick tests. Bronchoprovocation test showed an early asthmatic response to cellulase extract. Serum specific IgE and specific IgG4 antibodies to cellulase were detected by enzyme-linked immunosorbent assay (ELISA). In order to further characterize the allergenic component of the extract, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and electroblotting studies were performed. Eight IgE binding components ranging from 6 to 97.5 kD were detected within the cellulase extract., Conclusion: These findings suggest that inhalation of cellulase can induce IgE-mediated bronchoconstrictions in employees working in the textile industry.

Although asthma is considered to be an inflammatory disease of the airways, neural mechanisms remain very important. Neural control of airways is far more complex than has been previously recognized. In addition to the classic neural pathways, the nonadrenergic, noncholinergic pathway has been described in the airways of animals and humans. Neuropeptides are present in sensory, parasympathetic, and sympathetic neurons in airways, and have been shown to have proinflammatory effects, such as increased mucus production, microvascular leakage, and smooth muscle contraction. Neuropeptides released from sensory nerves (eg, neurokinin A and substance P) mediate excitatory nonadrenergic, noncholinergic transmission, which causes bronchoconstriction and, possibly, bronchial hyperresponsiveness. Better understanding of neural mechanisms might provide a useful therapeutic approach in the future.

Background: There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma., Objective: This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histological abnormalities in asthmatics according to the severity of asthma., Methods: Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inflammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultrastructural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina., Conclusion: These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.