• Tuberculosis and Respiratory Diseases
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• v.84 no.1
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• pp.55-66
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• 2021

Background: Particulate matter 10 (PM₁₀; airborne particles <10 ㎛) inhalation has been demonstrated to induce airway and lung diseases. In this study, we investigate the effects of PM₁₀ inhalation on RNA expression in lung tissues using a murine model. Methods: Female BALB/c mice were affected with PM₁₀, ovalbumin (OVA), or both OVA and PM₁₀. PM₁₀ was administered intranasally while OVA was both intraperitoneally injected and intranasally administered. Treatments occurred 4 times over a 2-week period. Two days after the final challenges, mice were sacrificed. Full RNA sequencing using lung homogenates was conducted. Results: While PM₁₀ did not induce cell proliferation in bronchoalveolar fluid or lead to airway hyper-responsiveness, it did cause airway inflammation and lung fibrosis. Levels of interleukin 1β, tumor necrosis factor-α, and transforming growth factor-β in lung homogenates were significantly elevated in the PM₁₀-treated group, compared to the control group. The PM₁₀ group also showed increased RNA expression of Rn45a, Snord22, Atp6v0c-ps2, Snora28, Snord15b, Snora70, and Mmp12. Generally, genes associated with RNA splicing, DNA repair, the inflammatory response, the immune response, cell death, and apoptotic processes were highly expressed in the PM₁₀-treated group. The OVA/PM₁₀ treatment did not produce greater effects than OVA alone. However, the OVA/PM₁₀-treated group did show increased RNA expression of Clca1, Snord22, Retnla, Prg2, Tff2, Atp6v0c-ps2, and Fcgbp when compared to the control groups. These genes are associated with RNA splicing, DNA repair, the inflammatory response, and the immune response. Conclusion: Inhalation of PM₁₀ extensively altered RNA expression while also inducing cellular inflammation, fibrosis, and increased inflammatory cytokines in this murine mouse model.

• Tuberculosis and Respiratory Diseases
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• v.76 no.4
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• pp.169-174
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• 2014

Background: The Korean Obstructive Lung Disease (KOLD) Cohort Study is a prospective longitudinal study of patients with chronic obstructive pulmonary disease (COPD), asthma, or other unclassified obstructive lung diseases. It was designed to develop new classification models and biomarkers that predict clinically relevant outcomes for patients with obstructive lung diseases. Methods: Patients over 18 years old who have chronic respiratory symptoms and airflow limitations or bronchial hyper-responsiveness were enrolled at 17 centers in South Korea. After a baseline visit, the subjects were followed up every 3 months for various assessments. Results: From June 2005 to October 2013, a total of 477 subjects (433 [91%] males; 381 [80%] diagnosed with COPD) were enrolled. Analyses of the KOLD Cohort Study identified distinct phenotypes in patients with COPD, and predictors of therapeutic responses and exacerbations as well as the factors related to pulmonary hypertension in COPD. In addition, several genotypes were associated with radiological phenotypes and therapeutic responses among Korean COPD patients. Conclusion: The KOLD Cohort Study is one of the leading long-term prospective longitudinal studies investigating heterogeneity of the COPD and is expected to provide new insights for pathogenesis and the long-term progression of COPD.

• Tuberculosis and Respiratory Diseases
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• v.61 no.5
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• pp.433-439
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• 2006

Background: Although airway hyper-responsiveness is one of the characteristics of asthma. bronchial hyper-responsiveness has also been observed to some degree in patients with chronic obstructive pulmonary disease (COPD). Moreover, several reports have demonstrated that a number of patients have both COPD and asthma. The methacholine bronchial challenge test (MCT) is a widely used method for the detecting and quantifying the airway hyper- responsiveness, and is one of the diagnostic tools in asthma. However, the significance of MCT in differentiating asthma or COPD combined with asthma from pure COPD has not been defined. The aim of this study was to determine the role of MCT in differentiating asthma from pure COPD. Method: This study was performed prospectively and was composed of one hundred eleven patients who had undergone MCT at Chonbuk National University Hospital. Sixty-five asthma patients and 23 COPD patients were enrolled and their MCT data were analyzed and compared with the results of a control group. Result: The positive rates of MCT were 65%, 30%, and 9% in the asthma, COPD, and control groups, respectively. The mean $PC_{20}$ values of the asthma, COPD, and control groups were $8.1{\pm}1.16mg/mL$, $16.9{\pm}2.21mg/mL$, and $22.0{\pm}1.47mg/mL$, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT for diagnosing asthma were 65%, 84%, 81%, and 69%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MCT (ed note: please check this as I believe that these values correspond to the one $PC_{20}$ value. Please check my changes.) at the new cut-off points of$PC_{20}{\leq}16mg/ml$, were 80%, 75%, 78%, and 78%, respectively. Conclusion: MCT using the new cut-off point can be used as a more precise and useful diagnostic tool for distinguishing asthma from pure COPD.

• Tuberculosis and Respiratory Diseases
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• v.80 no.1
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• pp.11-20
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• 2017

Approximately one in four patients with chronic obstructive pulmonary disease (COPD) have asthmatic features consisting of wheezing, airway hyper-responsiveness or atopy. The Global initiative for Asthma/Globalinitiative for chronic Obstructive Lung Disease committee recently labelled these patients as having asthma-COPD overlap syndrome or ACOS. ACOS also encompasses patients with asthma, ${\geq}40$ years of age, who have been cigarette smokers (more than 5-10 pack years) or have had significant biomass exposure, and demonstrate persistent airflow limitation defined as a post-bronchodilator forced expiratory volume in 1 second ($FEV_1$)/forced vital capacity of <70%. Data over the past 30 years indicate that patients with ACOS have greater burden of symptoms including dyspnea and cough and show higher risk of COPD exacerbations and hospitalizations than those with pure COPD or pure asthma. Patients with ACOS also have increased risk of rapid $FEV_1$ decline and COPD mortality. Paradoxically, experimental evidence to support therapeutic decisions in ACOS patients is lacking because traditionally, patients with ACOS have been systematically excluded from therapeutic COPD and asthma trials to maintain homogeneity of the study population. In this study, we summarize the current understanding of ACOS, focusing on definitions, epidemiology and patient prognosis.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1210-1223
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• 2018

Background/Aims: The co-occurrence of obesity aggravates asthma symptoms. Diet-induced obesity increases helper T cell (TH) 17 cell differentiation in adipose tissue and the spleen. The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pravastatin can potentially be used to treat asthma in obese patients by inhibiting interleukin 17 (IL-17) expression. This study investigated the combined effects of pravastatin and anti-IL-17 antibody treatment on allergic inflammation in a mouse model of obesity-related asthma. Methods: High-fat diet (HFD)-induced obesity was induced in C57BL/6 mice with or without ovalbumin (OVA) sensitization and challenge. Mice were administered the anti-IL-17 antibody, pravastatin, or both, and pathophysiological and immunological responses were analyzed. Results: HFD exacerbated allergic airway inflammation in the bronchoalveolar lavage fluid of HFD-OVA mice as compared to OVA mice. Blockading of the IL-17 in the HFD-OVA mice decreased airway hyper-responsiveness (AHR) and airway inflammation compared to the HFD-OVA mice. Moreover, the administration of the anti-IL-17 antibody decreased the leptin/adiponectin ratio in the HFD-OVA but not the OVA mice. Co-administration of pravastatin and anti-IL-17 inhibited airway inflammation and AHR, decreased goblet cell numbers, and increased adipokine levels in obese asthmatic mice. Conclusions: These results suggest that the IL-17-leptin/adiponectin axis plays a key role in airway inflammation in obesity-related asthma. Our findings suggest a potential new treatment for IL-17 as a target that may benefit obesity-related asthma patients who respond poorly to typical asthma medications.

• Journal of Life Science
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• v.22 no.3
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• pp.298-305
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• 2012

The general term flavonoids is often used to categorize a family of natural compounds that are highly abundant in all higher plants, and which in recent years have attracted scientific interest as therapeutics. Lutein is a xanthophyll and one of 600 known naturally occurring carotenoids. It is found in green vegetables such as spinach and kale, and has been demonstrated to exert anti-inflammatory activities. However, its anti-allergic effect in the Th1/Th2 immune response is poorly understood. In this study, we attempt to determine whether lutein regulates inflammatory mediators in an ovalbumin (OVA)-induced murine asthma model. To address this, mice were sensitized and challenged with OVA, and then treated with lutein before the last OVA challenge. Administration of lutein significantly suppressed the OVA-induced airway hyper-responsiveness. It also resulted in a significant alleviation of the infiltration of inflammatory cells into the bronchoalveolar lavage. Additionally, lutein attenuated the increased expression of Th2 responses in OVA-challenged mice. These results demonstrate that lutein is a potent inhibitor that reduces Th2 immune responses. Furthermore, they show that the immunopharmacological function is mediated by a pathway that involves and is regulated by Th2 immune response.

• Herbal Formula Science
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• v.21 no.1
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• pp.36-50
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• 2013

Objectives : To clarify the possible effect of Lycium chinese Mill (LC)., Morus alba L (MA)., and Lycium chinese Mill. +Morus alba L. (LC+MA), we have examined their influence on the development of pulmonary eosinophilic inflammation in the asthmatic murine model. Methods : Female Balb/c mice (5weeks) were immunized on two different days (21 days and 7 days before inhalational exposure) by intraperitonial injections of 0.2ml alum-precipitated Ag containing $100{\mu}g$ of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 minutes/day on 3 days/week for 8 weeks (at a flow rate of 250 L/min, 2.5% ovalbumin in normal saline) and, LC, MA, and LC+MA (500 mg/kg) were orally administered 3 times per a week for 8 weeks. Results : The suppressive effect of LC, MA, and LC+MA were demonstrated by the accumulation of eosinophills into airways, with the reduction of eosinophil, total lung leukocytes numbers. These were correlated with the marked reduction of IL-5, IL-13 and IL-4 levels in the BALF and serum. OVA-specific IgE levels were also decreased in serum and BAL from these mice. LC, MA, and LC+MA decreased eosinophil CCR3 expression and CD11b expression in lung cells. Conclusions : These results indicate that LC, MA, and LC+MA have high inhibitory effects on airway inflammation and hyper-responsiveness in the asthmatic murine model. The suppression of IL-5, IgE, eosinophil CCR3 expression and CD11b expression, and the increase of IFN-${\gamma}$ production in BALF seem to contribute to this effect. Hence, the results indicated that LC, MA, and LC+MA could act as a immuno-modulator which possesses anti-inflammatory and anti-asthmatic property by modulating the imbalance between Th1 and Th2 cytokines.

• The Journal of Korean Medicine
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• v.25 no.1
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• pp.198-204
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• 2004

Backgrounds & Methods : Asthma is considered to be chronic inflammatory disease characterized by airway hyperresponsiveness and pulmonary eosinophilia. Recently, there has been many researches about asthma. IBS(Irritable Bowel Syndrome), PUD(peptic Ulcer disease) and GERD(gastroesophageal reflux disease) are the most common diseases of the gastrointestinal tract. Recent studies suggest that IBS, PUD and GERD are associated with bronchial hyper-responsiveness and bronchial asthma might be more prevalent in IBS and GERD patients than in control subjects. In addition, there are many comments about the interrelationship between the gastrointestinal problem and asthma in the oriental medical books. Actually, many oriental medical doctors don$^{\circ}$Øt consider the gastrointestinal condition when they deal with the asthmatic patients these days. So, we assessed the prevalence of gastrointestinal symptoms and histories in a cohort of patients with asthmatic symptoms. We evaluated 128 outpatients with asthmatic symptoms(60 males and 68 females, aged 13-75). All subjects enrolled completed the GSRS(Gastrointestinal Symptom Rating Scale). GSRS is an interview based rating scale consisting of 15 items for assessment of gastrointestinal symptoms in IBS and PUD developed by Jan Svedlund. Results : The limit of total score of GSRS in asthmatic patients is zero to 30. The number of patients with no GI symptoms is 66(51.5%). The number of patients with GSRS>5 is 62(48.4%), GSRS>10 is 24(18.8%), GSRS>15 is 8(6.25%). The number of patients with history of gastritis is 54(42.2%), gastric ulcer is 13(10.2%), gastroptosis is 8(6.25%), IBS is 6(4.68%), others is 6(4.68%). Conclusions : This study suggests that patients with bronchial asthma have an significant prevalence of gastrointestinal symptoms. Additional studies are needed to find the mechanism of the association between gastrointestinal symptoms and asthma.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.39-48
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• 2009

Objectives : To clarify the possible effect of JS (Juglans sinensis), PCF (Psoralea corylifolia L.), and J+P(JS+PCF), we examined their influence on the development of pulmonary eosinophilic inflammation in the asthmatic murine model. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by intraperitonial injections of 0.2 ml alum-precipitated Ag containing 100 ${\mu}$g of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 minutes/day on 3 days/week for 8 weeks (at a flow rate of 250 L/min, 2.5% ovalbumin in normal saline) and, JS, PCF and J+P (200 mg/kg, 400 mg/kg) were orally administered 3 times per week for 8 weeks. Results : The suppressive effects of JS, PCF, and J+P were demonstrated by the accumulation of eosinophils into airways, with the reduction of eosinophils and lung leukocytes. These were correlated with the marked reduction of IL-4, IL-5, IL-13 levels in the BALF and serum. OVA-specific IgE levels were also decreased in serum and BAL from these mice. And also JS, PCF, and J+P decreased eosinophilic CCR3 and CD11b expression in lung tissue. Conclusions : These results indicate that JS, PCF, and J+P have deep inhibitory effects on airway inflammation and hyper-responsiveness in the asthmatic murine model. The suppression of IL-5, IgE, and eosinophilils and the increase of IFN-${\gamma}$ production in BALF seem to contribute to these effects. Specially, esosinophils and TNF-a in J+P combination group were significantly reduced in BALF and lung tissue. Hence, the results indicated that JS, PCF, and J+P could act as an immuno-modulator which possesses anti-inflammatory and anti-asthmatic property by modulating the imbalance between Th1 and Th2 cytokines.

• BMB Reports
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• v.48 no.3
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• pp.178-183
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• 2015

Dendritic cells play an important role in determining whether na${\ddot{i}}$ve T cells mature into either Th1 or Th2 cells. We determined whether heat-shock protein X (HspX) purified from Mycobacterium tuberculosis regulates the Th1/Th2 immune response in an ovalbumin (OVA)-induced murine model of asthma. HspX increased interferon-gamma, IL-17A, -12 and transforming growth factor (TGF)-${\beta}$ production and T-bet gene expression but reduced IL-13 production and GATA-3 gene expression. HspX also inhibited asthmatic reactions as demonstrated by an increase in the number of eosinophils in bronchoalveolar lavage fluid, inflammatory cell infiltration in lung tissues, airway luminal narrowing, and airway hyper-responsiveness. Furthermore, HspX enhanced OVA-induced decrease of regulatory T cells in the mediastinal lymph nodes. This study provides evidence that HspX plays critical roles in the amelioration of asthmatic inflammation in mice. These findings provide new insights into the immunotherapeutic role of HspX with respect to its effects on a murine model of asthma.