• 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.

• 대한본초학회지
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• 제28권2호
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• pp.9-15
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• 2013

Objectives : The root of Codonopsis pilosula (Fr.) Nannf. (Codonopsis Pilosulae Radix) has been traditionally used as a oriental medicine with an anti-thrombotic, antidiabetic, anticancer, and anti-gastric ulcer effects and immunological adjuvant. In this study, we investigated the effect of 70% ethanol extract of Codonopsis Pilosulae Radix (CPR-E) on ovalbumin (OVA)-induced allergic responses in mice. Methods : Mice were sensitized (1, 8, and 15 days) with OVA and airway challenged(22, 24, 26, 28, and 30 days) to induced allergic responses. CPR-E extract at doses of 50 and 100 mg/kg/body weight was orally administered from days 21 to 30 consecutively. The levels of allergic mediators such as histamine, OVA-specific immunoglobulin (Ig) E, and Th1/Th2 cytokines such as IFN-${\gamma}$ and IL-4 were measured in the sera of mice by ELISA. The histological change of lung tissue was observed by hematoxylin and eosin (H&E) staining. Results : CPR-E extract significantly decreased the serum levels of histamine, OVA-specific IgE, and IL-4 compared with those of OVA control group, but significantly increased the serum level of IFN-${\gamma}$. Based on H&E staining, CPR-E extract inhibited the infiltration of inflammatory cells into lung tissues with histological changes. Conclusions : These results indicate that CPR-E extract has anti-inflammatory and anti-allergic responses through regulating the cytokine balance, suggesting that the extract may be useful for the treatment of allergic inflammatory diseases such as bronchial asthma and allergic rhinitis.

• 대한본초학회지
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• 제24권1호
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• pp.73-78
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• 2009

Objectives : In this study, we studied the effect of Pinellia Ternata (PT) on regulatory T cells and CD3+CCR3+ Th2 cells number in asthma model mice. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by i.p. injections of 0.2 $m\ell$ 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 min/day on 3 days/week for 12 weeks(at a flow rate of 250 L/min, 2.5％ ovalbumin in normal saline) and PT (400, 200 mg/kg) were orally administered 3 times a week for 8 weeks. After C57BL/6 mice were orally given of PT, the percentages, cell numbers, phenotype and function of CD4+CD25+Treg cells were determined by flow cytometry. Results : The cell numbers of CD4+CD25+Treg cell subsets were markedly increased in PT treated mice as reported. However, PT significantly reduced the CD3+CCR3+ Th2 cells in PBMC and lung of mice. Conclusions : These results indicate that PT has a deep inhibitory effect on asthma model mice by increase the number of regulatory T cells, and by reducing CD3+CCR3+ Th2 cells.

• Tuberculosis and Respiratory Diseases
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• 제86권3호
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• pp.158-165
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• 2023

Asthma is a chronic inflammatory airway disease that is characterized by variable airflow obstruction. The Korean Asthma Study Group of the Korean Academy of Tuberculosis and Respiratory Diseases has recently updated the Korean Asthma Guideline. This review summarizes the updated Korean Asthma Guideline. Asthma prevalence is increasing worldwide, and in Korea. Variable airflow obstruction can be confirmed by bronchodilator response or other tests, and should be established prior to the controller medication. A low-dose inhaled corticosteroid-formoterol is used to alleviate symptoms in all treatment step, and it can be used as a controller as well as reliever in steps 3-5. This approach is preferred, because it reduces the risk of severe exacerbations, compared to the use of short-acting β2-agonist as reliever. In severe asthma, phenotype/endotype based on the underlying inflammation should be evaluated. For type 2 severe asthma, the biologics should be considered.

• IMMUNE NETWORK
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• 제21권6호
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• pp.42.1-42.20
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• 2021

Eosinophils play critical roles in the maintenance of homeostasis in innate and adaptive immunity. Although primarily known for their roles in parasitic infections and the development of Th2 cell responses, eosinophils also play complex roles in other immune responses ranging from anti-inflammation to defense against viral and bacterial infections. However, the contributions of pattern recognition receptors in general, and NOD-like receptors (NLRs) in particular, to eosinophil involvement in these immune responses remain relatively underappreciated. Our in vivo studies demonstrated that NLRC4 deficient mice had a decreased number of eosinophils and impaired Th2 responses after induction of an allergic airway disease model. Our in vitro data, utilizing human eosinophilic EoL-1 cells, suggested that TLR2 induction markedly induced pro-inflammatory responses and inflammasome forming NLRC4 and NLRP3. Moreover, activation by their specific ligands resulted in caspase-1 cleavage and mature IL-1β secretion. Interestingly, Th2 responses such as secretion of IL-5 and IL-13 decreased after transfection of EoL-1 cells with short interfering RNAs targeting human NLRC4. Specific induction of NLRC4 with PAM3CSK4 and flagellin upregulated the expression of IL-5 receptor and expression of Fc epsilon receptors (FcεR1α, FcεR2). Strikingly, activation of the NLRC4 inflammasome also promoted expression of the costimulatory receptor CD80 as well as expression of immunoregulatory receptors PD-L1 and Siglec-8. Concomitant with NLRC4 upregulation, we found an increase in expression and activation of matrix metalloproteinase (MMP)-9, but not MMP-2. Collectively, our results present new potential roles of NLRC4 in mediating a variety of eosinopilic functions.

• Tuberculosis and Respiratory Diseases
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• 제87권3호
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• pp.329-337
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• 2024

Background: Fractional exhaled nitric oxide (FeNO) is known to useful biomarker for detecting eosinophilic airway inflammation. However, there is a lack of evidence regarding the role of FeNO in chronic obstructive pulmonary disease (COPD). We aimed to assess whether elevated FeNO and its impact on treatment change into an inhaled corticosteroid (ICS)-containing regimen and association with acute exacerbation (AE) in patients with COPD. Methods: We retrospectively analyzed 107 COPD patients without a history of asthma from March 2016 to December 2019. The patients whose FeNO value was more than 50 parts per billion (ppb) were defined into the high FeNO group. Multivariable analysis with logistic regression was used to identify factors associated with AE in COPD. Results: The median FeNO value was 32 ppb (interquartile range, 19 to 45) and 34 (20.0%) patients were classified as high FeNO group (median 74 ppb). In the high FeNO group, changes in inhaler treatment into an ICS-containing regimen occurred in 23 of 34 patients after the measurement of FeNO. In multivariate analysis, high FeNO was not a contributing factor for AE, but only the high blood eosinophil count (≥300 cells/µL) was associated with AE (adjusted odds ratio, 2.63; 95% confidence interval, 1.01 to 6.91; p=0.049). Conclusion: High FeNO value had a significant impact on the prescription of ICSs in COPD patients, but it did not show a significant association with AE either on its own or with changes in treatment.

• The Korean journal of internal medicine
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• 제39권4호
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• pp.659-667
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• 2024

Background/Aims: Sensitization to staphylococcal superantigens (SAgs) could contribute to asthma severity. However, its relevance with eosinophilic phenotype has not yet been clarified. This study aimed to investigate associations between serum specific IgE levels to SAg and eosinophilic airway inflammation in adult asthmatics. Methods: The serum specific IgE levels to 3 SAgs, including staphylococcal enterotoxin A (SEA) and B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured by ImmunoCAP in 230 adult asthmatic patients and 50 healthy controls (HCs). Clinical characteristics and laboratory parameters, including serum total/free IgE, and 2 eosinophil-activation markers, eosinophil cationic protein (ECP), and eosinophil-derived neurotoxin (EDN), were analyzed according to blood eosinophil counts (BEC; 150 cells/µL) and serum specific IgE levels to 3 SAgs (0.35 kU/L). Results: Asthmatic patients showed higher serum specific IgE levels to 3 SAgs than HCs (p < 0.05 for all). The serum total/free IgE levels were significantly higher in asthmatics with positive IgE responses to 3 SAgs than those without (p < 0.05 for all). There were no significant differences in clinical parameters including age, asthma severity, comorbidities, or smoking according to IgE responses to 3 SAgs. Patients with positive IgE responses to SEB (not to SEA/TSST-1) had higher serum specific IgE levels to house dust mites and ECP/EDN as well as higher BEC with positive correlations between serum SEB-specific IgE levels and BEC/ECP/EDN (p < 0.05 for all). Conclusions: These findings suggest that serum SEB-specific IgE levels could contribute to eosinophil activation as well as IgE production in adult asthma.

• 생명과학회지
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• 제18권4호
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• pp.530-536
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• 2008

본 연구는 재조합 단백질 생산에 흔히 사용되는 P. fluorescens에 대한 공기 중 노출 시 염증작용이 의심되는 기전을 분석하기 위하여 인체 폐포 상피세포에서의 염증성 인자들 특히 IL-8, COX-2, MIC-1의 발현을 분석하고자 하였다. 균주 P. fluorescens에 대한 인체 폐포 상피세포 A549에서의 세포증식 억제효과를 밝혔고, 상피세포의 염증성 사이토카인으로서 대표적인 인터루킨 8의 발현에 대해서 분석결과. 균주 P. fluorescens및 재조합 균주에 의해 IL-8의 분비가 진핵세포대비 세균세포숫자 의존적으로 생성량이 증대되었다. 또한 점막 상피세포의 염증성 프로스타글란딘 생성에서 핵심적인 역할을 하는 cyclooxygenase-2 (COX-2)에 대해서 P. fluorescens 는 COX-2의 mRNA 발현이 소량 증진되었으나 실제 단백질의 양 및 전사의 변화는 없었다. 일반적으로 단핵구의 염증성 사이토카인 생성에 대하여 억제성 작용을 하는 macrophage inhibitory cytokine 1 (MIC-1)의 발현에 대해서 측정결과 유전자의 발현이 증대되는 효과는 미비하였으나, MIC-1 단백질의 processing에서 propeptide (${\sim}28\;kD$) 및 mature MIC-1 (${\sim}15\;kD$)로 분해 되어 MIC-1의 단백질 활성화가 증대되었다. 본 연구에서 보이는 MIC-1은 P. fluorescens에 의한 세포 생존율 억제작용에도 기여할 것으로 예측되며, IL-8에 의한 염증구의 recruitment 대한 억제작용이 예상되나, MIC-1의 활성이 과도하고 지속적으로 나타날 경우 조직의 손상도 가능성도 있다.

• Tuberculosis and Respiratory Diseases
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• 제51권3호
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• pp.211-223
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• 2001

연구배경 : 기관지에 리노 바이러스(rhinovirus) 감염은 기관지혈관 내피세포의 투과성을 증가시켜 저비중리포단백(LDL) 같은 혈장단백의 유입을 초래한다. 그런데 산화 저비중리포단백(oxidized LDL)은 단핵세포 대식식세포에서 IL-1, GM-CSF 분비를 유발하고 화학주성과 또한 CD11b/CD18 intergrin을 증가시키며 L-selectin 표현을 감소시킨다. 이러한 소견들은 산화 저비중리포단백이 proimflammatory 효과를 가진다는 것을 시사한다. 연구자들은 산화 저비중리포단백이 리노바이러스 감염시 기도에 과립구를 동원할것이라는 가설하에 산화 저비중리포단백에 의한 호중구와 호산구의 화학주성과 내피세포이동(transendothelial migration)에 대하여 연구하였다. 방 법 : 저비중리포단백을 20-24시간 동안 5mM $CU_2SO_4$로 산화 시키고 conjugated diens 형성 방법으로 234nm에서 산화 정도를 확인하였다. 과립세포들의 화학주성측정은 $3-5{\times}10_5$ 세포들을 transwell 필터에 놓고 $37^{\circ}C$, 5% $CO_2$ 1시간 항온배양후 이동한 세포들을 혈구계로 계산하였다. 과립세포들의 내피세포이동은 인체 미세폐혈관 내피세포(human pulmonary microvascular endothelial cell) 들을 transwell 필터에 배양후 호산구와 호중구를 화학주성물질과 함께 놓은 후 3시간 항온 배양후 이동한 세포들을 혈구계로 계산하였다. 결 과 : 산화 저비중리포단백은 호산구와 호중구에 화학주성이있고 화학주성정도는 저비중리포단백의 농도와 산화 정도에 비례하였다. 또한 산화 저비중리포단백은 과립구의 인체 미세폐혈관 내피세포이동을 농도에 비례히여 자극하였고 호중구가 호산구보다 낮은 농도의 산화 저비중리포단백에 예민하게 반응하였다. 결 론 : 리노바이러스 감염으로 혈관투과정 증가로 저비중리포단백의 유입과 산화를 유발하고 이 산화 저비중리포단백이 기관지 간질세포에 호중구와 호산구이동을 유발하는 한 기전이며 또한 이과립구들이 산화 저비중단백과 함께 기도 염증을 초래할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제61권4호
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• pp.330-338
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• 2006

연구배경: 만성폐쇄성폐질환은 기도염증으로 인한 기도폐쇄를 특징으로 하는 질환이지만, 질병의 경과중에 체중감소나 근위축 같은 전신증상을 동반하게 된다. 만성 염증과 산화 스트레스가 만성폐쇄성폐질환의 병인에 중요한 역할을 하므로 신체질량지수의 감소와 관련이 있을 것으로 추측할 수 있다. 연구자 등은 안정된 만성폐쇄성폐질환 환자에서 신체질량지수와 관련된 인자를 알아보기 위해 다음과 같은 연구를 시행하였다. 방 법: 안정된 만성폐쇄성폐질환 환자 53명(남:여=49:4, 평균나이=$68.25{\pm}6.32$)과 정상 대조군 33명을 대상으로 폐기능 검사를 실시하고 전신염증인자로 혈청 IL-6, TNF-$\alpha$를 측정하고 산화 스트레스 인자로 혈청 8-iso-prostaglandin $F_2{\alpha}$와 carbonyl protein을 측정하여 비교하였다. 또한 만성폐쇄성폐질환 환자를 신체질량지수에 따라 다시 3군(<18.5, 18.5-25, >25)으로 나누어 각각의 수치들을 비교하였고 만성폐쇄성폐질환의 중증도에 따라 신체질량지수를 비교하였다. 결 과: 만성폐쇄성폐질환 환자와 정상 대조군의 혈청에서 IL-6, TNF-$\alpha$, carbonyl protein은 유의한 차이가 없었으며 8-iso-prostaglandin $F_2{\alpha}$은 각각 $456.08{\pm}574.12pg/ml$, $264.74{\pm}143.15pg/ml$로 만성폐쇄성폐질환 환자에서 유의하게 높았다(p<0.05). 만성폐쇄성폐질환에서 신체질량지수의 차이에 따라 혈청 IL-6, TNF-$\alpha$, carbonyl protein과 8-iso-prostaglandin $F_2{\alpha}$은 유의한 차이를 보이지 않았다. 신체질량지수에 따른 환자의 $FEV_1$은 각각 $0.93{\pm}0.25L$, $1.34{\pm}0.52L$, $1.72{\pm}0.41L$로 신체질량지수가 낮을수록 $FEV_1$ 값도 감소하는 경향을 보였고(p=0.002, r=0.42), 최중증 만성폐쇄성폐질환 환자의 신체질량지수는 $19.8{\pm}2.57$로 중등증의 환자의 $22.6{\pm}3.14$에 비해 유의하게 낮았다(p<0.05). 결 론: 본 연구에서 안정된 만성폐쇄성폐질환 환자의 신체질량지수는 전신염증인자와 산화 스트레스의 정도와는 관련을 보이지 않았으나 기도폐쇄의 정도와는 관련이 있을 것으로 사료된다. 만성폐쇄성폐질환 환자에서 신체질량지수의 감소와 관련된 인자에 대해서는 추가적인 연구가 필요할 것으로 사료된다.