• Journal of Oral Medicine and Pain
• /
• 제43권1호
• /
• pp.16-20
• /
• 2018

Graft-versus-host disease (GVHD) is frequent complications of hematopoietic stem cell transplantation. In the chronic GVHD (cGVHD), the oral cavity is the most commonly affected region. The clinical manifestations include erythema, ulceration, lichenoid-hyperkeratotic change in oral mucosa, dry mouth, and limitation of mouth opening. The initial treatment strategy of oral cGVHD patients is topical corticosteroid therapy in various formulation. However, corticosteroid resistance appears in some patients. We report a case of a 25-year-old male patient with oral cGVHD, who has resistance to topical corticosteroid medication, treated with 0.03% tacrolimus ointment and low-dose doxycycline. The patient showed subjective and objective improvement without side effect.

• Tuberculosis and Respiratory Diseases
• /
• 제85권1호
• /
• pp.18-24
• /
• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Tuberculosis and Respiratory Diseases
• /
• 제81권1호
• /
• pp.80-87
• /
• 2018

Background: Asthma is a disease of chronic airway inflammation with heterogeneous features. Neutrophilic asthma is corticosteroid-insensitive asthma related to absence or suppression of $T_H2$ process and increased $T_H1$ and/or $T_H17$ process. Macrolides are immunomodulatory drug that reduce airway inflammation, but their role in asthma is not fully known. The purpose of this study was to evaluate the role of macrolides in neutrophilic asthma and compare their effects with those of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin (OVA) and lipopolysaccharides (LPS). Clarithromycin (CAM) and/or dexamethasone (DXM) were administered at days 14, 15, 21, 22, and 23. At day 24, the mice were sacrificed. Results: Airway resistance in the OVA+LPS exposed mice was elevated but was more attenuated after treatment with CAM+DXM compared with the monotherapy group (p<0.05 and p<0.01). In bronchoalveolar lavage fluid study, total cells and neutrophil counts in OVA+LPS mice were elevated but decreased after CAM+DXM treatment. In hematoxylin and eosin stain, the CAM+DXM-treated group showed less inflammation additively than the monotherapy group. There was less total protein, interleukin 17 (IL-17), interferon ${\gamma}$, and tumor necrosis factor ${\alpha}$ in the CAM+DXM group than in the monotherapy group (p<0.001, p<0.05, and p<0.001). More histone deacetylase 2 (HDAC2) activity was recovered in the DXM and CAM+DXM challenged groups than in the control group (p<0.05). Conclusion: Decreased IL-17 and recovered relative HDAC2 activity correlated with airway resistance and inflammation in a neutrophilic asthma mouse model. This result suggests macrolides as a potential corticosteroid-sparing agent in neutrophilic asthma.

• Clinical and Experimental Pediatrics
• /
• 제60권6호
• /
• pp.167-174
• /
• 2017

Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006-2007, 2011, and 2015-2016. Although MPP is known to be a mild, self-limiting disease with a good response to macrolides, it can also progress into a severe and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant MPP has rapidly increased, especially in Asian countries, recently reaching up to 80%-90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point mutation in domain V of 23S rRNA with substitutions mainly detected at positions 2063 and 2064 of the sequence. The excessive use of macrolides may contribute to these mutations. MRMP can lead to clinically refractory pneumonia, showing no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. Refractory MPP is characterized by an excessive immune response against the pathogen as well as direct injury caused by an increasing bacterial load. A change of antibiotics is recommended to reduce the bacterial load. Tetracyclines or quinolones can be alternatives for treating MRMP. Otherwise, corticosteroid or intravenous immunoglobulin can be added to the treatment regimen as immunomodulators to downregulate an excessive host immune reaction and alleviate immune-mediated pulmonary injury. However, the exact starting time point, dose, or duration of immunomodulators has not been established. This review focuses on the mechanism of resistance acquisition and treatment options for MRMP pneumonia.

• Childhood Kidney Diseases
• /
• 제2권1호
• /
• pp.26-33
• /
• 1998

목적 : 신증후군 환아에서 입원시 신피질 에코도의 증가가 병리조직검사와 관련이 있는지 알아보고, 부신피질 호르몬에 대한 반응 여부를 예측하는데 이용될 수 있는지 알아 보고자 다음 연구를 고안하였다. 방법 : 고려대학교 부속 병원 소아과에 입원한 환아 중 입원시 24시간뇨에서 2g 이상의 단백뇨를 보인 환아 69명을 대상으로 하였다. 입원 당시의 신장초음파검사상 신피질 에코도 증가와 신장 조직검사상 간질의 부종이나 섬유화, 세관 위축, 사구체 경화 및 염증 세포 침윤과의 상관 관계를 조사하였다. 그리고 조직검사로 확인된 일차성 신증후군 환아에서 신피질 에코도의 증가가 최근에 재발한 신증후군의 부신피질호르몬에 대한 반응도 및 조직검사 소견과 관련이 있는지 조사하였다. 결과 : 1. 대상아 69명중 남아가 49명 여아가 20명이었고, 연령은 1세에서 15세의 분포를 보였으며 7-9세가 20명으로 가장 많았다. 2. 신장조직검사는 46예에서 시행되었으며 미세 변화성 신증후군 20예, 국소성 분절성 사구체 경화증 7예, 막성 사구체 신염 2예, 막성 증식성 사구체 신염 1예, 연쇄상 구균 감염 후 사구체 신염 2예, IgA 신염이 5예, Henoch-Schonlein 자반증 신염 6예, 전신성 홍반성 낭창 1예, Alport 증후군이 2예이었다. 3. 신장조직검사가 시행되었던 46예중 사구체의 전반성 경화나 세뇨관 위축이 있는 경우는 신피질 에코도가 의의있게 증가하였으나 (P<0.05), 간질의 부종이나 섬유화, 염증 세포의 침윤 등은 신피질 에코도의 증가와 관련이 없었다. 4. 조직검사로 확인된 일차성 신증후군 환아 30명중 9예에서 입원시 신피질 에코도의 증가를 보였으며 이중 7명이 부신피질호르몬 치료에 반응을 보이지 않아서 신피질 에코도의 증가와 부신피질 호르몬 치료에 대한 저항성과는 유의한 관계를 보였으나(P<0.05), 신피질 에코도의 증가와 조직검사 소견과는 유의한 관계를 보이지 않았다. 결론 : 단백뇨를 보이는 환아에서 입원시 신피질 에코도의 증가는 사구체의 전반적인 경화나 세뇨관 위축에 의한 것으로 생각되며, 일차성 신증후군에서 입원시 신피질 에코도의 증가는 부신피질 호르몬 치료에 대한 저항을 나타내는 지표로 이용할 수 있는 것으로 생각된다.

• The Korean Journal of Pain
• /
• 제30권4호
• /
• pp.281-286
• /
• 2017

Background: Magnetic resonance imaging (MRI) of the spine is the preferred diagnostic tool for pathologic conditions affecting the spine. However, in patients receiving epidural corticosteroid injection (ESI) for treatment of spinal diseases, there is a possibility of misreading of MR images because of air or fluid in the epidural space after the injection. Therefore, we defined the characteristics of abnormal changes in MRI findings following an ESI in patients with low back pain. Methods: We reviewed the medical records of 133 patients who underwent MRI of the lumbar spine within 7 days after ESI between 2006 and 2015. All patients were administered an ESI using a 22-gauge Tuohy needle at the lumbar spine through the interlaminar approach. The epidural space was identified by the loss of resistance technique with air. Results: The incidences of abnormal changes in MRI findings because of ESI were 54%, 31%, and 25% in patients who underwent MRI at approximately 24 h, and 2 and 3 days after ESI, respectively. Abnormal MRI findings included epidural air or fluid, needle tracks, and soft tissue changes. Epidural air, the most frequent abnormal finding (82%), was observed in 41% of patients who underwent MRI within 3 days after injection. Abnormal findings due to an ESI were not observed in MR images acquired 4 days after ESI or later. Conclusions: Pain physicians should consider the possibility of abnormal findings in MR images acquired after epidural injection using the interlaminar approach and the loss of resistance technique with air at the lumbar spine.

• Pediatric Infection and Vaccine
• /
• 제31권1호
• /
• pp.37-45
• /
• 2024

목적: 본 연구는 마크로라이드 불응성 마이코플라즈마 폐렴(macrolide-unresponsive Mycoplasma pneumoniae pneumonia, MUMP)의 임상 양상 및 관련 인자와 2차 치료제로서 doxycycline (DXC), tosufloxacin (TFX) 및 corticosteroid (CST) 사용 후 해열되는 데까지 걸리는 시간의 차이를 평가하고자 하였다. 방법: 2018년 7월부터 2020년 2월까지 노원을지대학교병원에 발열 및 호흡기 증상과 함께 흉부 엑스선 상 폐렴 소견이 있어 입원하여 마이코플라즈마 폐렴으로 진단받은 18세 이하의 환자들의 의무기록을 후향적으로 분석하였다. M. pneumoniae의 23S 리보솜 RNA (23S rRNA) 유전자의 점 돌연변이 유무로 마크로라이드 내성을 확인하였다. MUMP는 마크로라이드계 항생제 치료 개시 후 72시간 이상 발열(≥38.0℃)이 지속된 경우로 임상적으로 정의하였다. MUMP의 경우, CST를 추가한 군과 이차 항생제인 DXC 또는 TFX로 변경한 군으로 구분하였다. 결과: 총 157명의 마이코플라즈마 폐렴 환자 중 MUMP 군은 83명(52.9%)이었으며, C-반응단백(C-reactive protein, CRP)의 상승(3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), 흉부 X-선상 대엽/분절성 폐렴, 흉수(56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032) 그리고 23S rRNA 유전자의 점 돌연변이(96.4% vs. 64.6%, P<0.001) 가 MUMP와 유의한 연관성을 보였다. MUMP 군 83명 중 30명(36.1%)은 DXC로, 38명(45.8%)은 TFX로 항생제를 변경하였고 15명(18.1%)은 CST를 추가하였다. 2차 치료로 변경 이후 발열 호전까지 걸린 평균 시간을 각 군별로 비교하였을 때 CST 군이 DXC, TFX 군보다 발열 호전까지의 시간이 유의하게 짧았고(10.3±12.7 vs. 19.4±17.2 시간, P=0.043; 10.3±12.7 vs. 25.0±20.1 시간, P=0.003), DXC 군과 TFX 군 사이에는 유의한 차이를 보이지 않았다(19.4±17.2 vs. 25.0±20.1 시간, P=0.262). 결론: CRP의 높은 상승과 흉부 X-선 상 대엽/분절성 폐렴 및 흉막 삼출, 그리고 23S rRNA A2063G 점 돌연변이가 마크로라이드 불응성과 유의한 연관이 있었다. CST 환자군에서 DXC나 TFX 환자군에 비하여 더 빠른 발열 호전을 보였다. 향후 MUMP에 대한 최적의 2차 치료제를 결정하기 위해 더 큰 규모의 전향적 연구가 필요하다.

• IMMUNE NETWORK
• /
• 제21권3호
• /
• pp.19.1-19.18
• /
• 2021

Clinical and molecular phenotypes of asthma are complex. The main phenotypes of adult asthma are characterized by eosinophil and/or neutrophil cell dominant airway inflammation that represent distinct clinical features. Upper and lower airways constitute a unique system and their interaction shows functional complementarity. Although human upper airway contains various indigenous commensals and opportunistic pathogenic microbiome, imbalance of this interactions lead to pathogen overgrowth and increased inflammation and airway remodeling. Competition for epithelial cell attachment, different susceptibilities to host defense molecules and antimicrobial peptides, and the production of proinflammatory cytokine and pattern recognition receptors possibly determine the pattern of this inflammation. Exposure to environmental factors, including infection, air pollution, smoking is commonly associated with asthma comorbidity, severity, exacerbation and resistance to anti-microbial and steroid treatment, and these effects may also be modulated by host and microbial genetics. Administration of probiotic, antibiotic and corticosteroid treatment for asthma may modify the composition of resident microbiota and clinical features. This review summarizes the effect of some environmental factors on the upper respiratory microbiome, the interaction between host-microbiome, and potential impact of asthma treatment on the composition of the upper airway microbiome.

• 한국임상약학회지
• /
• 제14권1호
• /
• pp.11-23
• /
• 2004

Although most children with idiopathic nephrotic syndrome respond to corticosteroid therapy, many responders show steroid dependency and frequent relapse. In these children, one of the major problems is the serious side effects resulting from continuous steroid therapy. Thus, this study was conducted to assess the therapeutic efficacy and safety of six-month cyclosporine treatment with the low-dose deflazacort therapy in children with nephrotic syndrome. Thirty children with steroid dependence (SD), frequent relapse (FR) and steroid resistance (SR) were enrolled in this study. They were treated with 6-month oral cyclosporine $(Cypol-N^{(R)})$ plus the low-dose deflazacort $(Calcort^{(R)})$ therapy at Samsung Medical Center from September 2002. The dosage of cyclosporine was started at 5 mg/kg/day and was monthly adjusted to maintain clinical remission and/or a trough blood level, while deflazacort dosage was reduced gradually. Clinical evaluation and monitoring of cyclosporine toxicity were performed every $2\sim4$ weeks. Outcomes were compared to the latest sir-month period of steroid only therapy before cyclosporine treatment. Student's t-test and ANOVA were used for statistical analysis. Out of 28 children with SD and FR, 23 $(82.1\%)$ sustained remission, and 5 $(17.9\%)$ experienced 1 or 2 relapses during therapy. Out of 2 children with SR, 1 child sustained remission, and 1 child showed no response. The mean duration of remission and occurrence of relapse were significantly improved (p <.0001). In addition, the mean dosage of steroid was significantly reduced (p=.003). Although a number of adverse effects occurred in this study, they were not so serious as to necessitate discontinuation of the therapy. No nephrotoxicity was observed. Twenty out of the 28 children who had been in remission relapsed after withdrawal of cyclosporine. Fifteen of these children showed relapse within a month. These results demonstrated that the combination of cyclosporine with the low-dose deflazacort was efficient and safe in children with SD and FR during the six-month treatment. However, further studies are necessary in order to resolve the problem of high relapse rate after discontinuation of cyclosporine.