• IMMUNE NETWORK
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• 제22권6호
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• pp.45.1-45.15
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• 2022

Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.

• Tuberculosis and Respiratory Diseases
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• 제46권2호
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• pp.175-184
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• 1999

연구배경: 알레르기성 기관지 천식은 가역적인 기도폐색과 기관지의 과민성을 동반하는 기도의 만성적인 호산구성 염증성 질환으로서 기도의 염증발현에 관여하는 세포는 여러가지가 있지만 Th 림프구는 cytokine을 분비하여 염증반응을 조절하는 중요한 역할을 하고 있다. Th 림프구는 cytokine의 분비양상에 따라 Th1 림프구와 Th2 림프구로 나뉘어지며 Th1 림프구는 지연형 과민반응과 결핵균이나 바이러스 감염등에 대한 방어작용 그리고 종양에 대한 숙주반응에 관여하고 Th2 림프구는 즉시형 과민반응과 알레르기성 천식과 같은 알레르기성 질환 그리고 기생충 감염등에 대한 방어작용에 관여한다. Th1 림프구와 Th2 림프구는 서로 길항작용을 하는 것으로 알려지고 있어 대표적인 Th1 림프구 매개 질환인 결핵과 Th2 림프구 매개질환인 알레르기성 기관지 천식은 서로의 발생을 억제할 것으로 추정되며 알레르기성 기관지 천식환자에서는 Th2 림프구의 기능이 항진되어 Th1 림프구의 기능이 억제되고 반대로 Th1 림프구의 기능이 정상인 집단에서는 알레르기성 천식환자에 비해 Th2 림프구의 기능이 저하되어 있을 것으로 추정된다. 방 법: 정상 대조군과 알레르기성 천식환자군, 그리고 내인성 천식환자군에서 투베르쿨린 피부반응의 양상을 실시하여 지연형 과민반응의 양상을 관찰하고 혈청 IgE의 농도와 말초혈액 호산구 수를 조사하였다. 그리고 Th1 림프구에서 주로 생산되는 cytokine인 IFN-$\gamma$와 IL-12, Th2 림프구에서 주로 생산되는 IL-4, IL-5, IL-10의 혈청 농도를 측정하였다. 결 과: 투베르쿨린 피부반응의 양성율은 알레르기성 천식환자군이 내인성 천식환자군에 비해 투베르쿨린 피부반응에 대한 양성율이 유의하게 낮았으며(p<0.05), 투베르쿨린 피부반응의 정도는 내인성 천식환자군에 비하여 알레르기성 천식환자에서 유의하게 감소되어 있었다 (p<0.05). IL-4와 IL-10은 알레르기성 천식환자군에서 다른 두 군에 비하여 통계적으로 유의하지 않았으나 증가되어 있었고 IL-5는 알레르기성 천식환자군에서 다른 두 군에 비하여 유의하게 증가되어 있었다 (p<0.01). IL-12와 IFN-$\gamma$는 알레르기성 천식환자군과 내인성 천식환자군에서 정상 대조군에 비하여 유의하게 감소되어 있었다(p<0.05). 알레르기성 천식환자군에서 말초 혈액 호산구 수와 혈청 IgE 농도는 정상 대조군에 비하여 유의하게 증가하여 있었다(p<0.05). 알레르기성 천식환자에서 말초혈액 호산구 수는 혈청 IgE(r=0.737, p=0.003), IL-5(r=0.352, p=0.038), IL-10(r=0.827, p=0.001)과 서로 유의한 상관관계를 보이면서 증가하고 있었다. 전체적으로 Th2 cytokine인 IL-5와 IL-10의 혈청 농도는 서로 유의한 상관관계를 나타내고 있었고(r=0.340, p=0.046), IL-12와 IFN-$\gamma$ 혈청 농도도 서로 유의한 상관관계를 나타내고 있었다(r=0.593, p=0.001). 결 론: 알레르기성 기관지 천식환자는 정상 대조군에 비하여 Th1 림프구의 기능이 저하되어 있었고 Th2 림프구의 기능은 항진되어 있었으며, 이러한 Th2 림프구의 기능 항진은 말초혈액 호산구 수와 혈청 IgE와 유의한 상관관계를 보이고 있어 Th2 림프구 기능 항진이 알레르기성 기관지 천식의 병인에 중요한 역할을 할 가능성이 있음을 알 수 있다.

• IMMUNE NETWORK
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• 제7권1호
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• pp.18-25
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• 2007

Background: Although glucocorticoids (GCs) are effective in controlling asthma in the majority of patients, a subset of asthmatics fails to demonstrate a satisfactory response, even to systemic GC therapy. This population is referred to as being "steroid-resistant". The actual mechanism underlying steroid resistance in asthma remains to be elucidated. Methods: We have investigated how dexamethasone (DEX) regulates asthmatic phenotypes in a murine model of asthma, in which mice received i.p. immunization twice, followed by two bronchoprovocations with aerosolized OVA with a one-week interval, which we have recently described. Results: Pretreatment with DEX resulted in an inhibition of NF-${\kappa}B$ activation in asthmatic lungs, and also inhibited bronchoalveolar lavage (BAL) levels of NF-${\kappa}B$-dependent cytokines such as TNF-${\alpha}$ and CC chemokines [eotaxin and monocyte chemotactic protein (MCP)-1]. DEX was effective in suppressing airway hyperresponsiveness (AHR) at 10 h, Th2-dependent asthmatic phenotypes such as airway eosinophilia, BAL levels of Th2 cytokines (IL-5 and IL-13), and mucin production. However, DEX failed to suppress BAL levels of CXC chemokines [macrophage inflammatory protein-2 (MIP-2) and keratinocyte-derived chemokine (KC)] and airway neutrophilia. Conclusion: Airway neutrophilia is among the phenomena observed in patients with severe GC-resistant asthma. This study will provide insight into the molecular basis for airway neutrophila seen in steroid-resistant asthma. Further studies are required to delineate the underlying mechanism of CXC chemokine expression in asthma.

• Clinical and Experimental Pediatrics
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• 제53권11호
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• pp.951-956
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• 2010

Purpose: To compare the profiles of the bronchodilator response (BDR) among children with asthma and/or allergic rhinitis (AR) and to determine whether BDR in these children is reduced by treatment with inhaled and/or nasal corticosteroid. Methods: Sixty-eight children with asthma (mean age, 10.9 years), 45 children with comorbid asthma and AR (mean age, 10.5 years), and 44 children with AR alone (mean age, 10.2 years) were investigated. After a 2-week baseline period, all children were treated with inhaled fluticasone propionate (either 100 or $250{\mu}g$ b.i.d., tailored to asthma severity) or nasal fluticasone propionate (one spray b.i.d. in each nostril) or both, according to the condition. Before and 2 weeks after starting treatment, all children were evaluated with spirometry and bronchodilator testing. BDR was calculated as a percent change from the forced expiratory volume in 1 second ($FEV_1$) at baseline. Results: The mean BDR was 10.3% [95% confidence interval (CI) 8.3-12.4%] in children with asthma, 9.0% (95% CI 7.3-10.9%) in subjects with asthma and AR, and 5.0% (95% CI 4.1-5.9%) in children with AR alone ($P$<0.001). After treatment, the mean BDR was reduced to 5.2% (95% CI 4.2-6.3%) ($P$<0.001) in children with asthma and to 4.5% (95% CI 3.5-5.5%) ($P$<0.001) in children with asthma and AR. However, children with rhinitis showed no significant change in BDR after treatment, with the mean value being 4.7% (95% CI 3.7-5.8%) ($P$=0.597). Conclusion: The findings of this study imply that an elevated BDR in children with AR cannot be attributed to nasal inflammation alone and highlights the close relationship between the upper and lower airways.

• 동의생리병리학회지
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• 제20권3호
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• pp.581-589
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• 2006

These studies were investigated the effects of Gamicheungpyehwadam-tang (CPHDT) on immune-cell regulation in association with bronchial asthma in OVA-induced mouse model. The administration of 400 mg/kg CPHDT significantly reduced the number of total cells in lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. The administration of 400 mg/kg CPHDT significantly reduced $CD3^+,{\;}CD19^+$and $CD3^+,{\;}CD69^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model. CPHDT significantly reduced $CD3^+/CCR3^+,{\;}CD4^+,{\;}B220^+/IgE^+$, and $CD3^+/DX5^+$ cell numbers separated from lung, peripheral lymph node and spleen in OVA-induced bronchial asthma mouse model in a dose dependent manner, However, CPHDT significantly reduced $CD8^+$ cell numbers from only lung and spleen. The administration of CPHDT significantly reduced $NK^+$ cell numbers separated from lung of OVA-induced bronchial asthma mouse model in all concentrations, but 200 mg/kg CPHDT reduced $NK^+$ cell numbers separated from peripheral lymph node. These results suggest that CPHDT has anti-asthma and anti-allergy effects. In addition to, CPHDT may be useful treatment of asthma based on the further studies about the individual efficacy search of the components of CPHDT and the adding of variety drugs to CPHDT.

• 한국환경보건학회지
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• 제45권6호
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• pp.613-621
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• 2019

Objectives: This study was performed to examine the relationship between health behaviors, living environment, and asthma in adolescents in Korea. Methods: Information on adolescents' characteristics, including demographic factors, health behaviors, and doctor's diagnosis of asthma was obtained from the Korean Youth Risk Behavior Web-based Survey (2015). In total, 68,043 middle and high school students participated. Environmental characteristics, including city park area and outdoor PM₁₀ concentrations in 2015 were obtained from the Korean Statistical Information Service. The adolescents' and environmental characteristics were merged by local information. Multiple logistic regression models were used to investigate the risk factors affecting asthma in adolescents. Results: The prevalence of asthma in adolescents in 2015 was 8.8%. In the multiple logistic regression analysis, adolescents who were male, attended middle school, suffered obesity, experienced tobacco smoking, had physical activity levels of 2 to 4 days, had higher stress levels, and lived in areas with outdoor PM₁₀ concentrations more than 47 ㎍/㎥ were more likely to have asthma, while adolescents who had middle levels of family economic status were less likely to do so. Conclusions: The fact that PM₁₀ concentration can affect asthma is an important point in this study. Risk factors identified in this study could be used as basic data for the prevention and management of asthma in Korea.

• Journal of Preventive Medicine and Public Health
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• 제34권1호
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• pp.61-72
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• 2001

Objectives : To evaluate the hypothesis that increasing ambient levels of ozone or particulate matter are associated with increased emergency room visits for asthma and to quantify the strength of association, if any, between these. Methods : Daily counts of emergency room visits for asthma, air quality, and weather data were collected from hospitals with over 200 beds and from monitoring Stations in Seoul, Korea from 1994 through 1997. Daily counts of emergency mom visits for asthma attack were analyzed using a general additive Poisson model, with adjustment for the effects of secular trend, seasonal variation, Sunday and holiday, temperature, and humidly, according to levels of ozone and particulate matter. Results : The association between daily counts of emergency room visits for asthma attack and ozone levels was statistically significant in summer(from June to August), and the RR by unit inclement of 100 ppb ozone was 1.30(95% CI = $1.11\sim1.52$) without lag time. With restriction of the period from April to September in 1996, the RR was 1.37(95% CI = $1.06\sim1.76$), and from June to August in 1995, the RR was 1.62(95% CI = $1.12\sim2.35$). In the data for children$(5\sim14yr)$, the RR was 2.57(95% CI = $1.31\sim5.05$) with restriction of the period from April to September in 1997. There was no Significant association between TSP levels and asthma attacks, but a slight association was seen between PM10 levels and asthma attacks in a very restricted period. Conclusion : There was a statistically significant association between ambient levels of ozone and daily counts of emergency room visits for asthma attack. Therefore, we must make efforts to effectively minimize air pollution, in order to protect public health.

• Journal of Preventive Medicine and Public Health
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• 제39권4호
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• pp.309-316
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• 2006

Objectives: Korean epidemiological studies have used reduced samples according to the subject's characteristics, such as the health services provided, the historical note with asthma, and age, to examine the acute effect of air pollution on asthma using the Korean National Health Insurance records. However, there have been few studies on whether the effects shown in these reduced samples are different from those of all samples. This study compared the effects of air pollution on asthma attacks in three reduced samples with those of entire samples. Methods: The air pollution data for $PM_{10},\;CO,\;SO_2,\;NO_2,\;and\;O_3$, and weather conditions including temperature, relative humidity, and air pressure in Seoul, 2002, were obtained from outdoor monitoring stations in Seoul. The emergency hospital visits with an asthma attack in Seoul, 2002 were extracted from the Korean National Health Insurance records. From these, the reduced samples were created by health service, historical notes with asthma, and age. A case-crossover design was adopted and the acute effects of air pollution on asthma were estimated after adjusting for weather, time trend, and seasonality. The model was applied to each reduced sample and the entire sample. Results: With respect to the health service, the effects on outpatients were similar to those for the total sample but were different for inpatients. These similar effect sizes were also observed in the reduced samples according to the historical note with asthma and age. The relative risks of $PM_{10},\;CO,\;SO_2,\;NO_2,\;and\;O_3$, among the reduced and entire samples were 1.03, 1.04-1.05, 1.02-1.03, 1.04-1.06, and 1.10-1.17, respectively. Conclusions: There was no clear evidence to show a difference between the reduced samples and the entire samples.

• Molecules and Cells
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• 제44권8호
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• pp.580-590
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• 2021

Patients with severe asthma have unmet clinical needs for effective and safe therapies. One possibility may be mesenchymal stem cell (MSC) therapy, which can improve asthma in murine models. However, it remains unclear how MSCs exert their beneficial effects in asthma. Here, we examined the effect of human umbilical cord blood-derived MSCs (hUC-MSC) on two mouse models of severe asthma, namely, Alternaria alternata-induced and house dust mite (HDM)/diesel exhaust particle (DEP)-induced asthma. hUC-MSC treatment attenuated lung type 2 (Th2 and type 2 innate lymphoid cell) inflammation in both models. However, these effects were only observed with particular treatment routes and timings. In vitro co-culture showed that hUC-MSC directly downregulated the interleukin (IL)-5 and IL-13 production of differentiated mouse Th2 cells and peripheral blood mononuclear cells from asthma patients. Thus, these results showed that hUC-MSC treatment can ameliorate asthma by suppressing the asthmogenic cytokine production of effector cells. However, the successful clinical application of MSCs in the future is likely to require careful optimization of the route, dosage, and timing.

• Tuberculosis and Respiratory Diseases
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• 제85권3호
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• pp.227-236
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• 2022

Background: The use of low-dose inhaled corticosteroid-formoterol as reliever monotherapy has recently been recommended in the asthma treatment guidelines. However, the efficacy of this treatment strategy has not yet been determined during the stepping-down period in moderate asthma. This study aimed to evaluate the feasibility of reducing treatment to as-needed budesonide-formoterol (BFM) in moderate asthma with complete remission. Methods: We randomly assigned 31 patients (8 males and 23 females with a mean age of 57.2 years) with complete remission of asthma by inhaled BFM (160/4.5 ㎍) twice daily to receive BFM (160/4.5 ㎍) as needed (16 patients), or budesonide (BUD) (200 ㎍) twice daily (15 patients). The study was an open-label study done for 48 weeks, with the primary outcome as the cumulative percentages of patients with treatment failure (asthma exacerbation or loss of asthma control or lack of satisfaction after using medications) in the two groups. Results: Six patients (42%) using as-needed BFM had treatment failure, as compared with three patients (21.4%) using BUD maintenance (hazards ratio for as-needed BFM, 1.77; 95% confidential interval, 0.44-7.12; p=0.41). The changes in forced expiratory volume in 1 second were -211.3 mL with as-needed BFM versus -97.8 mL with BUD maintenance (difference, 113.5 mL; p=0.75) and the change in fractional exhaled nitric oxide was significantly higher in both groups, at 8.68 parts per billion (ppb) in the as-needed BFM group and 2.5 ppb. in the BUD maintenance group (difference, 6.18 ppb; p=0.049). Conclusion: Compared with BUD maintenance, there were no significant differences in treatment failure rate in patients who received as-needed BFM during the stepping down period in moderate asthma. However, they showed reduced lung function and relapsed airway inflammation. The results are limited by imprecision, and further large RCTs are needed.