• Molecules and Cells
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• 제46권9호
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• pp.558-572
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• 2023

Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

• 한국컴퓨터정보학회:학술대회논문집
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• 한국컴퓨터정보학회 2021년도 제64차 하계학술대회논문집 29권2호
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• pp.297-298
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• 2021

본 논문은 만성폐쇄성 폐 질환이 흡연, 대기오염으로 많은 질환자가 발생하여 재활운동을 필요로 하는 추세이다. 현재 측정 도구와 재활운동 도구가 분리되어 질환 진단은 한정된 시설을 이용해야만 하고 재활운동 또한 상시 진행할 수 없어 질환을 확인하기 어려운 실정이다. 이에 평상시 착용하는 이너형태에 재활운동 의류를 개발하여 올바른 호흡을 돕는 근육군이 동원하여 복식호흡을 유도하고 흉식호흡 시 웨어러블기기를 통해 인지하게 돕는다. 이 결과 일상 속 지속 가능한 재활운동을 바탕으로 가슴 벽의 호흡근육 활동을 감소시키고 복부 근육군을 개선하는 것으로 폐 기능을 증진시킬수 있는 언더웨어 개발을 제안하고자 한다.

• Tuberculosis and Respiratory Diseases
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• 제63권6호
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• pp.480-485
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• 2007

연구배경: 만성폐쇄성폐질환은 여러 중요한 사망 원인 중 전세계적으로 유일하게 유병률이 증가하고 있는 질환이다 만성폐쇄성폐질환은 폐 이외의 다른 장기에도 영향을 끼치는 전신 질환으로 이해되고 있다. 본 연구는 폐활량 검사에서 기류 폐쇄 유무에 따른 호흡기 증상 빈도와 검사실 성적에 대해 알아보고자 하였다. 방 법: 2001년 국민건강영양조사와 같이 시행된 국가 단위 만성폐쇄성폐질환 유병률 조사에 참여한 대상으로 연구가 수행되었다. 본 연구는 폐활량 검사를 실시하여 GOLD 진단 기준으로 기류 폐쇄가 있는 대상과 없는 대상으로 구분하여 총 콜레스테롤, 혈액요소질소, 크레아티닌, 혈색소, 적혈구용적율, 공복 혈당, 고밀도 콜레스테롤, 중성지방의 평균값의 차이가 있는지를 알아 보았고 설문 조사를 통한 호흡기 증상의 빈도를 확인하였다. 결 과: 총 2,217명이 연구대상에 포함되었다. 이 중 GOLD 진단 기준에 따라 기류 폐쇄가 있는 대상이 288명, 기류 폐쇄가 없는 대상이 1,929명이었다. 호흡곤란을 느낀 적이 있다고 대답하였으나 기류 폐쇄의 유무에 따른 차이는 없었다. 기류 폐쇄가 있는 연구 대상들은 기류 폐쇄가 없는 대상들보다 객담, 기침, 천명음 등의 증상을 더 많이 호소하였다. 폐기능이 나쁠수록 호흡기 증상을 호소하는 연구 대상이 통계적으로 유의하게 더 많았다. 혈색소, 적혈구용적률의 평균값은 기류 폐쇄가 있는 군에서 더 높게 측정 되었으며 고밀도 콜레스테롤의 평균값은 기류 폐쇄가 있는 군이 통계적으로 낮게 측정 되었다. 총콜레스테롤, 중성지방, 혈액요소질소, 크레아티닌, 공복 혈당의 평균값은 기류 폐쇄 유무에 상관 없이 양군간에 차이는 없었다. 결 론: 기류 폐쇄가 없는 연구 대상에 비해 기침, 객담, 천명음과 같은 호흡기 증상의 경험 빈도가 많았고 혈액 검사에서 혈색소, 적혈구용적률의 평균값은 컸으며 고밀도 콜레스테롤의 평균값은 낮았다. 운동시 호흡곤란의 빈도, 총 콜레스테롤, 중성지방, 공복 혈당, 총 콜레스테롤, 혈액요소질소, 크레아티닌의 평균값은 기류 폐쇄의 유무와 상관 없었다.

• Tuberculosis and Respiratory Diseases
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• 제70권4호
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• pp.293-300
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• 2011

Chronic obstructive pulmonary disease (COPD) is a substantially under-diagnosed disorder, and the diagnosis is usually delayed until the disease is advanced. However, the benefit of early diagnosis is not yet clear, and there are no guidelines in Korea for doing early diagnosis. This review highlights several issues regarding early diagnosis of COPD. On the basis of several lines of evidence, early diagnosis seems quite necessary and beneficial to patients. Early diagnosis can be approached by several methods, but it should be confirmed by quality-controlled spirometry. Compared with its potential benefit, the adverse effects of spirometry or pharmacotherapy appear relatively small. Although it is difficult to evaluate the benefit of early diagnosis by well-designed trials, several lines of evidence suggest that we should try to diagnose and manage patients with COPD at early stages of the disease.

• IMMUNE NETWORK
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• 제24권2호
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• pp.3.1-3.23
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• 2024

Cigarette smoke extract (CSE)-treated mouse airway epithelial cells (MAECs)-derived exosomes accelerate the progression of chronic obstructive pulmonary disease (COPD) by upregulating triggering receptor expressed on myeloid cells 1 (TREM-1); however, the specific mechanism remains unclear. We aimed to explore the potential mechanisms of CSE-treated MAECs-derived exosomes on M1 macrophage polarization and pyroptosis in COPD. In vitro, exosomes were extracted from CSE-treated MAECs, followed by co-culture with macrophages. In vivo, mice exposed to cigarette smoke (CS) to induce COPD, followed by injection or/and intranasal instillation with oe-TREM-1 lentivirus. Lung function and pathological changes were evaluated. CD68⁺ cell number and the levels of iNOS, TNF-α, IL-1β (M1 macrophage marker), and pyroptosis-related proteins (NOD-like receptor family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-1 recruitment domain, caspase-1, cleaved-caspase-1, gasdermin D [GSDMD], and GSDMD-N) were examined. The expression of maternally expressed gene 3 (MEG3), spleen focus forming virus proviral integration oncogene (SPI1), methyltransferase 3 (METTL3), and TREM-1 was detected and the binding relationships among them were verified. MEG3 increased N6-methyladenosine methylation of TREM-1 by recruiting SPI1 to activate METTL3. Overexpression of TREM-1 or METTL3 negated the alleviative effects of MEG3 inhibition on M1 polarization and pyroptosis. In mice exposed to CS, EXO^-CSE further aggravated lung injury, M1 polarization, and pyroptosis, which were reversed by MEG3 inhibition. TREM-1 overexpression negated the palliative effects of MEG3 inhibition on COPD mouse lung injury. Collectively, CSE-treated MAECs-derived exosomal long non-coding RNA MEG3 may expedite M1 macrophage polarization and pyroptosis in COPD via the SPI1/METTL3/TREM-1 axis.

• 대한한방내과학회지
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• 제45권1호
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• pp.11-30
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• 2024

Objectives: This study evaluated the effects of Ssanghwa-tang (SHT) on lung injury and muscle loss in a COPD mouse model. Methods: C57BL/6 mice were challenged with cigarette smoke extract and lipopolysaccharide, and then treated with two concentrations of SHT (250 and 500 mg/kg). After sacrifice, the bronchoalveolar lavage fluid (BALF) or lung tissue was analyzed by cytospin, ELISA, real-time PCR, flow cytometry analysis, and H&E and Masson's trichrome staining. The grip strength of COPD mice was measured using a grip strength meter. The running time of COPD mice was measured by a treadmill test. Muscle tissue of the quadriceps was stained with H&E and Masson's trichrome staining. Results: SHT significantly inhibited the increase in neutrophil numbers in BALF and significantly decreased immune cell activity in BALF and lung tissue. It also significantly inhibited the increase in TNF-α, IL-17, and MIP2 in BALF. Real-time PCR analysis revealed that the mRNA expression of TNF-α, IL-17, MIP2, and TRPV1 in lung tissue showed a significant decrease compared with the control group. Lung tissue damage was significantly reduced in the histological analysis. The grip strength and running time of the COPD mice showed a significant decrease compared with the control group. In histological staining, SHT was found to reduce the damage to muscle tissue. Conclusions: This study indicates that SHT can be used as a therapeutic agent for COPD patients by inhibiting lung injury and muscle loss.

• Journal of Pharmaceutical Investigation
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• 제40권4호
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• pp.231-236
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• 2010

This study was to fabricate the porous poly(lactide-co-glycolide) (PLGA) microparticles with anthocyanin (as a model antioxidant) for pulmonary drug delivery. The highly porous PLGA microparticles were prepared by the waterin-oil-in-water ($W_1/O/W_2$) multi-emulsion method, followed by the decomposition of ammonium bicarbonate (AB) in $W_1$ phase to the base of ammonia, carbon dioxide and water vapor at $50^{\circ}C$, making a porous structure in PLGA microparticles. Herein, hyaluronate (HA), a viscous polysaccharide, was incorporated in the porous microparticles for sustained anthocyanin release. In in vitro release studies, the anthocyanin release from the porous microparticles with HA continued up to 24 hours, while the porous microparticles without HA released 80 wt.% of encapsulated anthocyanin within 2 hours. In addition, these microparticle are expected to be effectively deposited at a lung epithelium due to its high porosity (low density) and avoid alveolar macrophage's uptake in the lung due to its large particle size. We believe that this system has a great pharmaceutical potential as a long acting antioxidant for relieving the oxidative stress in chronic obstructive pulmonary disease (COPD).

• Journal of Ginseng Research
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• 제46권3호
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• pp.496-504
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• 2022

Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

• 한국임상약학회지
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• 제32권3호
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• pp.155-165
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• 2022

Background: Chronic obstructive pulmonary disease (COPD) is not completely reversible and requires long-term management with appropriate treatment. This study aimed to analyze trends in treatment regimens and medication costs for COPD patients using a national claims database. Methods: We conducted this analysis using National Patient Sample data from the Health Insurance Review and Assessment Service covering the period from 2015 to 2018. We have constructed a dataset comprising COPD disease classification codes J43.x and J44.x (based on KCD-7 code, J43.0 was excluded) and compiled a list of drugs fitting current guidelines. To identify trends, we calculated frequency, ratio, and compound annual growth rate (CAGR) using the numbers of prescriptions and patients. Results: The number of COPD patients was 7,260 in 2018, slightly decreased from 2015. Most of these COPD patients were aged 60 or older and included a high proportion of males (72.2%; 2018). The number of patients prescribed inhaled medications increased gradually from 2015 to 2018 (9,227 (47.1%); 2015, 9,285 (51.5%); 2018), while the number of patients prescribed systemic beta-agonists and Xanthines has decreased since 2015 (CAGR -14.7; systemic beta-agonist, -5.8; Xanthines). The per capita cost of medication has increased by 0.4% (KRW 206,667; 2018, KRW 204,278; 2015) annually during the study period. Conclusion: This study showed that treatment with inhaled medications had continuously increased in accord with changing guidelines, but oral medications were still widely used. It is necessary to emphasize the importance of inhaled medications in treating COPD to reduce additional economic burden through appropriate medication use.

• Tuberculosis and Respiratory Diseases
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• 제62권5호
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• pp.382-388
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• 2007

연구배경: 저산소증을 동반한 COPD 환자에서 인지기능 장애를 보이는 것은 잘 알려져 있다. 그러나 저산소증이 없는 COPD 환자에서의 인지기능에 대해서는 논란의 여지가 있다. 또한, COPD 환자는 수면장애를 동반하는 것으로 알려져 있다. 저자들은 저산소증이 없는 COPD 환자들의 인지기능을 평가하고, 인지기능 장애를 가진 COPD 환자들에서 수면장애가 얼마나 나타나는지 알아보았다. 방 법: 90% 이상의 동맥혈 산소 포화도를 가진 28명의 COPD 환자를 대상으로 연구를 시행하였으며, 환자의 평균 나이는 70.7세였다. 대조군은 건강검진을 위해 내원한 33명의 건강성인을 대상으로 하였고, 대조군의 평균 나이는 69.5세였다. 모든 환자 및 대조군은 the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease(CERADK)를 이용하여 신경인지기능을 평가하였다. 결 과: COPD 환자군은 단어목록회상(p=0.03)과 단어목록재인(p=0.006) 항목에서 대조군과 비교하여 유의하게 낮은 점수를 보였다. 9명의 환자에서 유의미한 인지기능 장애를 가지고 있었으며, 이 중 7명의 환자에서 수면다원검사를 시행한 결과, 5명의 환자에서 시간당 5회 이상의 apnea-hypopnea index를 보였다. 7명의 환자에서 동맥혈 산소 포화도 감소 지수 및 평균 사지 운동 지수는 각각 3.6/시간과 38.6/시간이었다. 결 론: 이 연구는 저산소증이 없는 COPD 환자에서 언어기억 장애를 가진다는 것을 시사하며, 이렇게 인지기능 장애를 가진 COPD 환자들이 수면장애를 동반하고 있어 이에 관한 추가연구의 필요성이 제시되었다.