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Background: Current management practices and outcomes in weaning from invasive mechanical ventilation are poorly understood. We aimed to describe the epidemiology, management, timings, risk for failure, and outcomes of weaning in patients requiring at least 2 days of invasive mechanical ventilation. Methods: WEAN SAFE was an international, multicentre, prospective, observational cohort study done in 481 intensive care units in 50 countries. Eligible participants were older than 16 years, admitted to a participating intensive care unit, and receiving mechanical ventilation for 2 calendar days or longer. We defined weaning initiation as the first attempt to separate a patient from the ventilator, successful weaning as no reintubation or death within 7 days of extubation, and weaning eligibility criteria based on positive end-expiratory pressure, fractional concentration of oxygen in inspired air, and vasopressors. The primary outcome was the proportion of patients successfully weaned at 90 days. Key secondary outcomes included weaning duration, timing of weaning events, factors associated with weaning delay and weaning failure, and hospital outcomes. This study is registered with ClinicalTrials.gov, NCT03255109. Findings: Between Oct 4, 2017, and June 25, 2018, 10 232 patients were screened for eligibility, of whom 5869 were enrolled. 4523 (77·1%) patients underwent at least one separation attempt and 3817 (65·0%) patients were successfully weaned from ventilation at day 90. 237 (4·0%) patients were transferred before any separation attempt, 153 (2·6%) were transferred after at least one separation attempt and not successfully weaned, and 1662 (28·3%) died while invasively ventilated. The median time from fulfilling weaning eligibility criteria to first separation attempt was 1 day (IQR 0–4), and 1013 (22·4%) patients had a delay in initiating first separation of 5 or more days. Of the 4523 (77·1%) patients with separation attempts, 2927 (64·7%) had a short wean (≤1 day), 457 (10·1%) had intermediate weaning (2–6 days), 433 (9·6%) required prolonged weaning (≥7 days), and 706 (15·6%) had weaning failure. Higher sedation scores were independently associated with delayed initiation of weaning. Delayed initiation of weaning and higher sedation scores were independently associated with weaning failure. 1742 (31·8%) of 5479 patients died in the intensive care unit and 2095 (38·3%) of 5465 patients died in hospital. Interpretation: In critically ill patients receiving at least 2 days of invasive mechanical ventilation, only 65% were weaned at 90 days. A better understanding of factors that delay the weaning process, such as delays in weaning initiation or excessive sedation levels, might improve weaning success rates. Funding: European Society of Intensive Care Medicine, European Respiratory Society.

BACKGROUND: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB). METHODS: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included. RESULTS: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P

Background: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype–phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF). Methods: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDR plus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital. Results: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrugresistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti- TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF. Conclusions: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.

Background The Glasgow Prognostic Score (GPS) reflects the host systemic inflammatory response and is a validated, independent prognostic factor for various malignancies. We investigated the clinical significance of the GPS in patients with tuberculosis (TB) pleurisy, focusing on treatment outcomes including paradoxical response (PR). Methods This was a retrospective study performed between January 2010 and December 2015 in two referral and university hospitals in South Korea, with intermediate incidences of TB. In all, 462 patients with TB pleurisy were registered in the study. The patients were classified into three groups based on GPS score, as follows: (I) GPS of 2, elevated CRP level (>1.0 mg/dL) and hypoalbuminemia (

Objectives We investigated the effect of long-term treatment with azithromycin on the pathogenesis of chronic asthma with airway remodeling. Methods Six-week-old-BALB/c mice were sensitized with ovalbumin (OVA) combined with lipopolysaccharide (LPS) for 1 month, then challenged with OVA for 3 months. Azithromycin at 75 mg/kg was administered via oral gavage five times a week during the challenge period. Inflammatory cells, T helper 2 cytokines in bronchoalveolar lavage fluid (BAL) fluid, and airway hyperresponsiveness (AHR) were measured. Parameters related to airway remodeling were evaluated. The levels of neutrophil elastase, Interleukin (IL)-8, and BRP-39 (human homologue YKL-40) were assessed. The expression of MAPK and NF-κB signaling were investigated. Results Long-term treatment with azithromycin improved AHR and airway inflammation compared with the OVA and the OVA/LPS groups. The concentrations of IL-5 and IL-13 in the OVA/LPS group decreased significantly after azithromycin administration. The levels of neutrophil elastase and IL-8, as surrogate markers of neutrophil activation, were reduced in the azithromycin group compared with the OVA/LPS group. Goblet cell hyperplasia and the smooth muscle thickening of airway remodeling were attenuated after azithromycin treatment. The expression of MAPK/NF-kappaB signal and the level of BRP-39 in the lung decreased remarkably in the OVA/LPS with azithromycin-treated group. Conclusions This study suggests that in a murine model of chronic asthma, long-term azithromycin treatment ameliorates not only airway inflammation but also airway remodeling by influencing on neutrophilc-related mediators, BRP-39 and MAPK/NF-κB signal pathways. Macrolide therapy might be an effective adjuvant therapy in a chronic, severe asthma with remodeling airway.

The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells.Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot. The concentrations of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit.Cell growth in PC9 and HCC827 cells was synergistically suppressed by co-treatment with gefitinib and linsitinib. Gefitinib did not affect H1975 cell growth; however, linsitinib suppressed cell proliferation. Co-treatment with gefitinib and linsitinib inhibited pAKT and pERK, and linsitinib treatment profoundly reduced IGF-1-induced pIGF-1R expression in PC9 and HCC827 cells. Dual treatment increased the number of Annexin-V-positive HCC827 and H1975 cells, and expression of cleaved caspase 3 and cleaved PARP increased in H1975 cells following linsitinib treatment. Gefitinib inhibited HIF-1α and VEGF expression in HCC827 cells, and linsitinib inhibited VEGF production in H1975 cells.IGF-1R TKIs had modest anti-tumor efficacy and their effects were explained by blocking the EGFR and IGF-1R pathway in IGF-1R expressing EGFR-sensitive cells. IGF-1R TKI had pro-apoptotic activity and inhibited cellular growth in EGFR-resistant cells.

Background and objective Peptide nucleic acid (PNA)-mediated real-time polymerase chain reaction clamping was recently developed to improve mutation detection sensitivity. Pleural effusion could be a good sample candidate for mutation analysis. To establish if PNA clamping could be used to detect KRAS mutation in particular in pleural effusion, we analysed its diagnostic performance. Methods We studied 57 patients with malignant effusion. KRAS mutation was evaluated in samples of matched tumour tissue, cell block, pleural effusion and serum using PNA clamping and direct sequencing. Results The detection rate of KRAS mutation using pleural effusion was 14% for PNA clamping and 10.5% for direct sequencing. The κ coefficient between the two methods was 0.76 (P value

The aim of this study was to measure the level of nerve growth factor (NGF) in bronchial specimens from humans and to determine whether it correlated with not only clinical characteristics of asthma such as percent eosinophils, Th2 cytokine levels, and pulmonary function, but also metallopeptidase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1).Fifty-three people participated; 42 had asthma. The participants underwent bronchoscopy and the specimens were analyzed. The participants' clinical data including pulmonary function tests were reviewed.Bronchoalveolar lavage fluid (BALF) from patients with asthma had a significantly higher level of NGF compared with that from participants without asthma. NGF level showed a positive correlation with the percentage of eosinophils in both BALF and serum. The concentration of NGF did not correlate with that of Th2 cytokines interleukin (IL)-4, IL-5, and IL-13 in BALF or parameters of pulmonary function including degree of airway hyperresponsiveness (ARH). The levels of MMP-9 and TIMP-1 in BALF were higher in asthma patients than in participants without asthma. The levels of NGF correlated with TIMP-1 levels but not with MMP-9 in the whole participants.This study shows that NGF correlates with levels of eosinophils, a major effector cell in asthma. The high expression of NGF and TIMP-1 in asthma patients and the moderate correlation between NGF and TIMP-1 in the entire group of asthma subjects suggest a possible association between NGF and TIMP-1, which may influence asthma pathogenesis.

Belotecan (Camtobell, CKD602) is a new camptothecin derivative antitumor agent that belongs to the topoisomerase inhibitors. The aim of this phase II study was to evaluate the efficacy and safety of single agent belotecan as a second-line therapy in patients with small cell lung cancer (SCLC). Patients who were previously treated for SCLC were entered into the study. Belotecan was given by daily intravenous infusion for five consecutive days, every three weeks. Twenty-five patients were enrolled in this study. On an intention-to-treat basis, belotecan induced an overall response rate of 24%, a median overall survival of 9.9 months, a median time to progression of 2.2 months, and a 1-year survival rate of 38.3%. Grade 3/4 neutropenia developed in 88.0% of patients and grade 3/4 thrombocytopenia in 40.0%. Nonhematologic toxicity of grade 3 or 4 was low. The results suggest that belotecan is relatively active and well tolerated as a second-line agent in patients with SCLC.

Background: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. Methods: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. Results: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. Conclusion: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Background: The tyrosine kinase inhibitor imatinib mesylate was developed as an inhibitor of the kinase activity of BCR-ABL. However, imatinib also has potent inhibitory activity against the platelet-derived growth factor receptor (PDGFR). Nilotinib is approved for treating patients with chronic myeloid leukemia showing resistance or intolerance to imatinib. Like imatinib, nilotinib selectively inhibits the tyrosine kinase activity of PDGFR. Objectives: We examined the effect of imatinib and nilotinib on acute lung injury and pulmonary fibrosis in a mouse model. Methods: Mice were treated by intratracheal instillation of bleomycin. Imatinib or nilotinib were administered by oral gavage. To study the early inflammatory and late fibrotic phases of lung injury, mice were sacrificed on days 3, 7, 14 and 21 after bleomycin instillation. Results: Histopathology showed that imatinib and nilotinib attenuated the extent of lung injury and fibrosis. The numbers of inflammatory cells and levels of IL-6, IL-1β and tumor necrosis factor-α were decreased in the imatinib and nilotinib groups on days 3 and 7. Imatinib and nilotinib therapy significantly reduced the levels of hydroxyproline on days 14 and 21, which was accompanied by decreased expression levels of transforming growth factor (TGF)-β1 and PDGFR-β. Imatinib and nilotinib also significantly reduced the expression levels of the genes for TGF-β1 and platelet-derived growth factor (PDGF). Imatinib and nilotinib treatment also significantly inhibited the PDGF-induced proliferation of lung fibroblasts in vitro. When imatinib or nilotinib was given 7 days after the instillation of bleomycin, only nilotinib attenuated pulmonary fibrosis. Conclusions: Imatinib and nilotinib attenuated bleomycin-induced acute lung injury and pulmonary fibrosis in mice. In a therapeutic model, nilotinib showed more potent antifibrotic effects than imatinib.

Tranilast has been used in allergic diseases because of its inhibitory effect on mast cells; it also has an anti-fibrotic effect in several diseases. Pentoxifylline (PTX), a methylxanthine derivative, is a potent anti-inflammatory drug that is known to manifest its effect through the inhibition of Th1 cytokine, but with an uncertain effect on Th2 cytokine. Seven-week-old female BALB/c mice were studied as a chronic asthma model. The mice were challenged with house dust mite (HDM) antigen for 7 weeks. Each group of mice was given an intraperitoneal injection of tranilast, PTX, or tranilast plus PTX before antigen administration. In this mouse model of chronic asthma, tranilast, and PTX each had an inhibitory effect on airway remodeling as well as on airway hyperresponsiveness (AHR) and airway inflammation. The improved events of these drugs were related with the inhibition of the Th2 cytokine IL-13 and TGF-beta 1. Immunohistochemical analysis showed that decreases in the peribronchial trichrome stained area in each treatment group were associated with improvements in the peribronchial smooth muscle hyperplasia, collagen type I, and collagen type III deposition. These drugs could have potential beneficial effects on chronic asthma, especially with respect to airway remodeling.

저자들은 급성호흡곤란을 주소로 내원한 류마티스 관절염 환자에서 임상소견과 흉부 방사선소견, 기관지폐포세척액 및 경기관지폐생검을 통해 methotrexate에 의한 간질성 폐렴 1예를 진단하였기에 문헌 고찰과 함께 보고하는 바이다. 【Methotrexate is commonly used in rheumatoid arthritis as an anti-inflammatory agent, but treatment with methotrexate can lead to severe side effects, especially pulmonary complication. Interstitial pneumonitis is one of the most important pulmonary adverse effects of methotrexate and most patient present with a subacute febrile illness and peripheral eosinophilia is seen in about a half of patients. Almost all patients have abnormal chest roentgenograms and bibasilar interstitial infiltration with alveolar pulmonary consolidations is the most characteristic finding. Interstitial inflammation with mononuclear cell infiltration is a characteristic pathologic feature and findings that suggest acute hypersensitivity pneumonitis, such as bronchiolitis, granuloma formation with giant cells, and infiltration with eosinophils are often present. Methotrexate-induced pneumonitis is a potentially life threatening and unpredictable complication but it is difficult to make a definite diagnosis in the absence of high index of clinical suspicion. Early recognition and appropriate management may avoid the serious outcome. Herein we report a case of methotrexate-induced pneumonitis in a patient with rheumatoid arthritis.】

Takayasu’s arteritis is a chronic inflammatory disease that primarily affects large vessels, such as the aorta and its main branches. Pulmonary artery is often involved in Takayasu’s arteritis, but only a few cases have been reported in which pulmonary artery involvement occurred as the initial clinical manifestation. We report one patient who was referred to our institution with the provisional diagnosis of chronic thromboembolic pulmonary hypertension and subsequently diagnosed with Takayasu’s arteritis involving the pulmonary artery. (Tuberculosis and Respiratory Diseases 2004, 56:677-682)

Primary pulmonary hypertension (PPH) is a rare, progressive and incurable disease, which is characterized by an increase in the pulmonary artery pressure without a demonstrable cause. The most common presenting symptom is dyspnea on exertion, with other symptoms comprising of chest pain, syncope and hemoptysis. The diagnosis is one of exclusion of any of the known causes of pulmonary hypertension. When associated with pregnancy, the maternal mortality ranges from 30 to 50%. Because pregnancy and labor are very serious problems for patients with PPH, the available evidence suggests that pregnancy when afflicted with PPH should be avoided. In account the case of a 33- year old patient, reporting with massive hemoptysis, and diagnosed with PPH during her twenty seventh week of gestation, is presented. She was treated with conservative management, including oxygen and a vasodilator, and underwent a pregnancy termination. However, due to aggravation of right heart failure, she presented with severe systemic hypotension and hypoxemia, and eventually died. This case is reported, with brief review of the literature. (Tuberc Respir Dis 2004; 57:66-67)

Background : Pulmonary hamartomas are the most common form of benign tumors, occurring in approximately 0.2% of routine autopsies. However, only a few reports on the clinical characteristics of pulmonary hamartoma in Korea have been published. Materials and Methods : The charts, X-rays and pathological specimens of 29 pulmonary hamartoma patients who were diagnosed by a pathological examination from 1990 to 1999 at the Catholic Medical Center were retrospectively reviewed. Results : The peak incidence of the tumor occurred in the sixth decade of life (37.5%). Seventeen patients (58.6%) were asymptomatic and 12 patients (41.4%) had symptoms. Chest discomfort was the most common symptom (31.0%). A total of 25 tumors (86.2%) were parenchymal, and 4 (13.8%) were endobronchial. Twenty cases were in the right lung and 9 cases were in the left lung (approximately 1:2.2). The RLL was the most commonly involved lobe (31.0%). Calcification was noted in 5 cases(19.2%) on a plain X-ray and in 5 cases (29.4%) on chest CT. Accompanied neoplasms were observed in 2 cases. Twenty-four hamartomas (82.8%) were diagnosed by a surgical resection and 4 cases(13.8%) were diagnosed by a fine needle aspiration biopsy. Twenty-six hamartomas (89.7%) were managed by a surgical resection. The follow up ranged from 4 to 55 months (mean, 19.6 months) and no recurrent pulmonary hamartomas were noted. Conclusion : Pulmonary hamartoma is more common in females and more commonly in the right lung. Calcification was noted only in 19.2% on a plain chest X-ray and 29.4% on a chest CT. No recurrent hamartomas had developed during the follow up period.

연구배경 : 기관지내시경은 호흡기질환의 진단과 치료에 유용한 도구로 널리 이용되고 있다. 그러나 상당수의 환자가 검사시 고통을 느끼거나 불안감을 느끼고 있어 이를 경감시켜주기 위한 전처치가 필요하다. 저자들은 전처치 약제로 midazolam의 안정성과 효과를 평가하고 또한 적절한 용량을 알아보고자 본 연구를 시행하였다. 방 법 : 연속적으로 기관지내시경을 시행한 180명의 환자를 대조군, midazolam 0.03 mg/kg군, midazolam 0.06 mg/kg군으로 분류하여 검사자와 내시경보조 간호사, 환자의 만족도를 비교하였다. 또한 검사중 혈압과 심박 및 산소포화도의 변화를 측정하였고 기침의 횟수와 lidocaine의 사용량을 측정하였다. 환자의 회복상태는 내시경검사 종료 후 10분간격으로 검사하였다. 결 과 : 각군간에 연령, 성별, 신장, 체중 및 검사시간의 차이는 없었다. 검사 전 및 검사중 혈압과 심박수 및 산소포화도는 각 군간에 유의한 차이가 없었으며 기침의 횟수, lidocaine의 투여량 역시 각 군간에 유의한 차이가 없었다. 기관지내시경 종료후 10분 내에 모든 환자에서 회복이 관찰되었다. 검사자 및 간호사의 만족도는 midazolam 0.03 mg/kg군에서 가장 높았으며 환자의 만족도는 midazolam 투여군 모두에서 대조군보다 높은 결과를 나타냈다. 결 론 : 기관지내시경 검사시 전처치로서 midazolam의 정맥투여는 안전한 방법으로 환자의 만족도를 증가시키며 저용량의 midazolam 투여는 의식하 진정작용을 통해 검사자의 만족도 또한 증가시키는 것으로 생각된다. 【Background : Bronchoscopy is an important diagnostic and a therapeutic tool in chest medicine. However, most patients feel that a bronchoscopy is an unpleasant procedure, and it is important to sedate the patients appropriately, particularly where repetitive examinations are required. Midazolam is a sedative drug with amnestic qualities and a rapid 2 hour half-life. This study have attempted to determine the safety, appropriate dosage, and the effect of midazolam premedication in patients who underwent a bronchoscopy. Methods : One hundred and eighty consecutive patients undergoing bronchoscopy were enrolled in this study. The patients received a midzolam doses of 0.03 mg/kg, 0.06 mg/kg, or a placebo. An additional dose of lidocaine, the total number of coughs, and the duration of the procedures were recorded with monitoring the the blood pressure, heart rate, and oxygen saturation. The level of satisfaction was assessed by the patient, bronchoscopist, and the nurse. Results : The blood pressure, pulse rates, oxygen saturation, number of coughs, lidocaine dose, and procedure time in the 3 groups were similar. There was a trend for the midazolam 0.03 mg/kg group to satisfy bronchoscopists more than the other two groups. The nurses' acceptability was lower in the midazolam 0.06 mg/kg group than the other groups. The patients' acceptablity was greater in both the midazolam 0.03 mg/kg and 0.06 mg/kg groups than in the control group. Conclusion : Sedation with low doses of intravenous midazolam is a safe technique for fiberoptic bronchoscopy with a low morbidity and high acceptable to patients and bronchoscopists.】

Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)- interleukin (IL)-, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF- inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF- MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF- and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL- and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF- and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

Background : Moxifloxacin is a newly developed drug which is more potent and safe compared to previous fluoroquinolones. This drug effectively eradicates organisms such as beta-lactamase-producing or other resistant bacteria. Moxifloxacin is known to be effective in treating respiratory infections such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniaeme, Legionella spp. and Mycoplasma pneumoniae. Methods : In a multicenter, randomized, open, comparative study, the efficacy and safety of oral moxifloxacin taken 400 mg once a day and clarithromycin taken 500 mg twice daily for 7 days were compared for the treatment of Korean patients with acute exacerbations of chronic bronchitis. Results : A total of 170 patients were enrolled, and they were divided into two groups: 87 in the moxifloxacin group and 83 in the clarithromycin group. Of those enrolled, 76 (35 for bacteriologic efficacy) in the moxifloxacin group and 77 (31 for bacteriologic efficacy) in the clarithromycin group were included in the efficacy analysis. All were included in the safety analysis. Clinical success was noted in 70 (92.1%) of 76 moxifloxacin-treated patients and 71 (92.2%) of 77 clarithromycin-treated patients. Bacteriologic success rate seemed to be higher in moxifloxacin group (73.5%) than in clarithromycin group (54.8%), but statistically insignificant (p=0.098). Drug susceptibility among organisms initially isolated was higher in moxifloxacin group on Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae (p

Background : Cytokines are chemical mediators that control and modulate many inflammatory processes. They work in different fashions in a variety of diseases. Discriminating between malignant effusion, tuberculous effusion, and parapneumonic effusion are crucial from the clinical view-point in Korea. In the current study, interferon-gamma (IFN-), soluble interleukin-2 receptor (IL-2R), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured for this purpose. Methods : Pleural fluids from patients with malignant disease, tuberculosis, parapneumonic effusion and lung empysema were collected and gauged using commercial ELISA kits. Results : 34 patients were enrolled in this study. Among these 15 cases were malignant effusions, 12 were tuberculosis pleurisy and 7 were parapneumonic effusion and lung empyema. The levels of cytokines measured in this study were as follows, in order of frequency, malignant effusion, tuberculous effusion, parapneumonic effusion and lung empyema. The levels of INF- were higher in tuberculous effusion than in malignant or parapneumonic effusion ( vs. vs. pg/ml, p>0.05). The levels of IL-2R were higher in tuberculous effusion than in malignant or parapneumoruc effusion ( vs. vs. pg/ml, p pg/ml in malignant effusion, pg/ml in tuberculous effusion, pg/ml in parapneumoruc effusion). IL-10 levels were higher in parapneumoruc effusion than in malignant or tuberculous effusions ( vs. vs. pg/ml, p

A 52-year-old woman was presented with 2-week history of increasing dyspnea and dry cough. The chest radiograph revealed bilateral reticular infiltrates. Radiographic infiltrates were rapidly progressed and symptoms from hypoxemia were aggravated. The patient was intubated and bronchoscopy with transbronchial lung biopsies was performed. Biopsies revealed lymphatic vessels plugged by nests of metastatic adenocarcinoma. She died 11 days after admission despite of intensive ventilatory support. We had difficulties in the diagnosis of lymphangitic lung carcinomatosis at initial presentation of her illness because the progression was unusually rapid. Lymphangitic lung carcinomatosis shoud should be included in the differential diagnosis of patients showing rapidly progressive interstitial radiographic findings. Also, transbronchial biopsy may be a useful tool to confirm the diagnosis.

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group , 12 hour group , 24 hour group , p) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group , 12 hour group , 24 hour group , p). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge (.. p. p

Background: Interleukin-12 (IL-12) can induce antitumor effects in vivo. This antitumor effect is associated with T cell infiltration but the effect of IL-12 on the steps of T cell migration into the tumor tissue has not been fully elucidated. This study focused on the effect of IL-12 on the tumor growth and the metastasis and on the expression of E-selectin, an adhesion molecule which is activated endothelial specific in its expression. In addition, we studied whether the expression of E-selectin is associated with the TNF-, a cytokine that its production is increased by IL-12 and has functions inducing a variety of adhesion molecules. Methods: Mice of C57BL/6 strain were injected with Lewis lung cancer cells followed by either IL-12, TNF-, or normal saline by intraperitoneal route. Twenty eight days after tumor cell inoculation, metastatic nodules of lung were enumerated and immunohistochemical staining of the subcutaneous tumors were performed with monoclonal antibodies to CD4, CD8, CD16, and E-selectin. In IL-12 treated mice, the subcutaneously implanted Lewis lung tumors were decreased in size and the metastases were also decreased in number compared to control mice. On tumor tissues, increased infiltration of CD4+, CD8+, and CD16+ cells were oberved in IL-12 treated mice compared to control mice. In control mice, E-selectin was absent on tumor vessels, but the expression of E-selectin was increased on tumor vessels of IL-12 treated mice. Administration of TNF- increased not only the expression of E-selectin but also infiltrations of CD4+, CD8+, and CD16+ cells on tumor tissues. Conclusions: These results demonstrate that IL-12 inhibits tumor growth and metastases through infiltrations of inflammatory cells in mouse model of Lewis lung carcinoma and E-selectin may playa role in inflammatory cell recruitment on tumor tissue following IL-12 administration. Also, TNF- may have a role as a mediator responsible for the IL-12 induced expression of E-selectin.

Background : Airway infiltration by inflammatory cells, particularly of eosinophils, is one of the characteristic features of asthma. Several mechanisms for the recruitment of eosinophil is focused on the CD4+ T lymphocyte for the preferential production of Th2-c1erived cytokines. Interleukin-10(IL-10) is identified cytokine with potent antiinflammatory activity. This molecule has been shown to inhibit the release of cytokine from inflammatory cells including Th2 cell, and also to inhibit eosinophil survival. We therefore attempted to determine whether decreased synthesis of IL-10 in the lung of bronchial asthma may contribute to inflammation that is characteristics of this dease. Method: Subjects were patients with bronchial asthma(n=23) and normal controls(n=11). IL-10 produced from peripheral mononuclear cell(PBMC) and in bronchoalveolar lavage(BAL) fluid was measured by ELISA method. Degree of bronchial inflammation was assessed by total cell counts and eosinophil percents in BAL fluid, eosinophil infiltration on bronchial biopsy tissue and for methacholine. Results: The IL-10 level produced by PBMC and in BAL fluid from patient with bronchial asthma were not different with normal controls(respectively, pg/ml, pg/ml for PBMC, pg/mL pg/ml for BAL fluid p>0.05). There were significant negative correlation between IL-10 in BAL fluid and eosinophil percents in BAL fluid or degree of eosinophil infiltration in bronchial biopsy (respectively r=-0.522, r=-0.4486 p for methacholine. There were no correlation between IL-10 production by PBMC and peripheral blood eosinophil counts or serum eosinophilic cationic protein levels(respectively r=0.1146, r=0.0769 p>0.05). Conclusion: These observation suggest that IL-10 may participate but not acts the crucial role in regulation of the airway inflammation in bronchial asthma.

Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p in patients with allergic asthma, in patients with intrinsic asthma and in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p

연구배경: 대량객혈을 치료하지 않는 경우 사망률이 50% 이상으로 매우 높은 것으로 알려져 있다. 대부분의 경우 출혈이 기관지 동맥에서 발생하고, 기관지 동맥색전술은 75-90% 의 환자에서 즉각적인 지혈효과를 가져오므로 대량객혈의 효과적인 치료방법으로 받아들여 지고 있다. 저자들은 대량 객혈환자에서 기관지 동맥 색전술의 유용성과 효과를 알아 보고자 하였고 또한, 성공적인 색전술후 재출혈에 관여 하는 인자를 알아보고자하였다. 방 법: 1990년 2월부터 1996년 7월 까지 가톨릭 의과대학 소속 7개 부속병원에 객혈을 주소로 내원하여 2 회 이상 객혈을 보이거나, 1 일 400-600cc 이상 대량 객혈을 보이는 환자에서 동맥색전술을 시행한 환자중에서 1년이상 경과관찰이 가능한 146명을 대상으로 하였다. 결 과: 기관지 동맥색전술을 시행한 환자는 남자 98예(67.1%), 여자48예(32.9%)였고, 객혈의 원인 질환으로는 폐결핵 및 이와 동반된 병변이 106예(72.6%)로 가장 많았다. 지혈에 사용된 색전물질로는 Ivalon을 단독으로 사용한 예가 58예(39.7%)로 가장 많았고, Gelfoam만 사용한 예는 52예(35.6%), 코일과 Gelfoam을 병용한 예는 24예(16.4%), Ivalon과 Gelfoam을 병용한 예는 9예(6.2%), 코일만 사용한 예는 3예(2.1%)이었다. 기관지 동맥색전술을 이용한 24시간 이내의 지혈의 성공률은 95%였으며, 추적관찰 중 객혈의 재발은 36예(24.7%)였고, 2 회이상 재발한 환자는 6예(4.1%)였다. 기관지 동맥색전술의 합병증은 40명(27.4%)의 환자에서 총 58 건수가 발생하였는데, 발열이 22 건(37.9%)으로 가장 많았고, 흉통 9건(32.8%), 두통 4건(6.9%), 오심 및 구토 3건(5.2%), 부정맥 2건(3.4%)순으로 나타났고, 기타 기침, 요통, 마비성장폐색, 배뇨장애, 하지감각 소실, 견갑골 통증, 저혈압, 두드러기등이 각각 1건씩 발생하였다. 초기 기관지동맥 조영술 소견상 색전의 대상이 양측성인 경우, 체측부동맥-폐동맥간 단락이 있는 경우, 신생혈관 형성, 동맥류, 출혈의 직접적인 소견인 조영제외 누출, 체측부동맥이 영양동맥으로 관여한 경우 등 이들 모두에서 재발군과 비재발군 사이에서 유의한 차이를 보이지 않았다(P>0.05). 원인 질환별, 지혈에 사용한 색전물질, 공동이 있는 경우, 국균종이 동반된 경우, 기관지 확장증이 동반된 경우, 폐기종이 동반된 경우 모두 재발군과 비재발군 사이에서 유의한 차이를 보이지 않았으나(P>0.05), 늑막에 병변이 있는 경우 양군 사이에 유의한 차이가 있었다(P 【Background : Massive and untreated hemoptysis is associated with a mortality of greater than 50 percent. Since the bleeding is from a bronchial arterial source in the vast majority of patients, embolization of the bronchial arteries(BAE) has become an accepted treatment in the management of massive hemoptysis because it achieves immediate control of bleeding in 75 to 90 percent of the patients. Methods: Between 1990 and 1996, we treated 146 patients with hemoptysis by bronchial artery embolization. Catheters(4, 5, or 7F) and gelfoam, ivalon, and/or microcoil were used for embolization. Results: Pulmonary tuberculosis and related disorders were the most common underlying disease of hemoptysis(72.6%). Immediate success rate to control bleeding within 24hours was 95%, and recurrence rate was 24.7%. The recurrence rate occured within 6 months after embolization was 63.9%. Initial angiographic findings such as bilaterality, systemic-pulmonary artery shunt, neovascularity, aneurysm were not statistically correlated with rebleeding tendency(P>0.05). Among Initial radiographic findings, only pleural lesions were significantly correlated with rebleeding tendency(P】

Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN- might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN- in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion() generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine in addition to the above parameters were also compared before and after IFN- treatment. IFN- was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects( vs cells, P treatment compared to initial values( vs cells, P, vs , P treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects( vs ), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN- treatment. However the means of serum sCD23 levels were not different before and after IFN- treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects( vs ), and slightly increased after IFN- treatment(). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN- treatment. And the levels of serum IgE were significantly decreased after IFN- treatment compared to initial values ( vs , P treatment, and the means of histamine were significantly increased after IFN- treatment compared to initial values ( vs , P may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN- may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

연구배경 : Erdosteine은 만성 기관지염 급성 악화시는 물론 만성 폐색성 기관지염 치료제로 개발된 Thiol 유도체로서 점액조절작용, 항산화작용이 있으며, 특히 위장관 부작용이 거의 없다. 본 연구에서는 현재 유효성 및 안전성이 입증되어 임상에서 많이 처방되고 있는 Ambroxol과의 비교임상연구를 통해 급성 및 만성 기관지염 환자에서 Erdosteine의 임상적 유용성을 알아보고자 하였다. 방 법 : 본 연구는 무작위 이중맹검 비교시험으로서 전향적 연구방법으로 수행되었다. 급 만성 기관지염으로 다량의 객담배출 혹은 객담배출곤란을 주증상으로 하는 80명을 무작위로 할당하여 Erdosteine 투여군에는 1일 2회, 1회 300mg, Ambroxol 투여군에는 1일 2회, 1회 30mg을 총 7일간 투여하였다. 1차 효과평가기준으로는 객담배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도, 호흡곤란을 포함한 자각증상이 평가되었고, 2차 효과평가기준으로는 동맥혈가스검사, 폐기능검사가 평가되었다. 안전성은 부작용과 임상병리검사로 평가하였다. 총 80명의 환자 중 61명(Erdosteine군 : 31명, Ambroxol군 : 30명)이 본 연구를 종료하였고 19명은 중도 탈락되었다. 결과의 분석은 paired t-test, ANOVA test, multivariate t2-test, Repeated measures analysis of covariance, two sample t-test, Loglinear-Logit model analysis, Fisher's exact test를 이 용하여 유의성을 검정하였다. 결 과 : 1) 두 군간의 환자배정에 있어서 인구학적, 임상적 특징은 차이가 없었다. 2) 동맥혈가스검사, 폐기능검사에서는 두 군간의 차이는 없었고, 자각증상에서는 Erdosteine군은 객담 배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도, 호흡곤란에서, Ambroxol군은 객담배출횟수, 객담량, 객담배출용이도, 객담점도, 기침정도에서 유의하게 호전을 보였다. 통계적으로 유의하지 않았으나 Erdosteine군이 Ambroxol군에 비해 더 유의하게 호전되는 경향을 보였다( $\alpha$ =0.05). 0.05). 3) 혈액학적검사, 혈액화학적검사 및 소변검사에서는 각 군 모두 임상적으로 의미있는 변화는 없었고 두 군간의 차이도 없었으며, 자각증상에서는 Ambroxol군에서만 4명이 연구 종료시까지 부작용이 소실되지 않았고 2명은 연구를 중단하였으나 두 군간의 차이는 없었다. 4) 각 약제의 최종효과평가에서 Erdosteine군은 31명 중 아주좋은효과 11명, 좋은효과 12명, 경도효과 6명, 무효과 2명, 악화 0명이었고 Ambroxol군은 30명 중 아주좋은효과 6명, 좋은효과 14명, 경도 효과 5명, 무효과 4명, 악화 1명이었으며 Erdosteine군이 Ambroxol군에 비해 증상이 개선될 확률이 약 2.5배만큼 높았다 (p 【Background : Erdosteine is a thiol derivative developed for the treatement of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis. Erdosteine has mucomodulating and antioxidant properties and especially exhibits excellent gastrointestinal tolerability. Methods : The study was conducted as a prospective evaluation, with 2 comparative groups orally treated with erdosteine 300mg (bid.) or ambroxol 30mg (b.i.d.) for 7 days and the design of trial was double-blind. The treatments have been assigned randomly to patients (n=80) with acute or chronic bronchitis. The primary end-point used to determine efficacy in this study was subjective symptoms including expectorating frequence, expectoration volume, expectorating difficulty, expectoration viscosity, cough intensity and dyspnea. The secondary end-points of efficacy was the result of arterial blood gas analysis and pulmonary function test. Safety was evaluated with adverse drug reactions and laboratory tests monitoring. 61 patients was included in the efficacy analysis, due to the fact that 19 patients drop-out for different reasons. The obtained values have been analyzed with paired Hest., ANOVA test., multivariate $t^2$ -test, repeated measures analysis of covariance, two sample t-test, loglinear-logit model analysis, Fisher's exact test. Results : 1) There was no significant difference on demographic data and vital signs between erdosteine and ambroxol treated groups. 2) The comparison between erdosteine and ambroxol treated groups showed no significant difference in improvement of each symptom in spite of the more favorable efficacy obtained with erdosteine. No difference on the contrary was observed for arterial blood gas analysis and pulmonary function test. 3) As safety is concerned, no clinical significant changes in laboratory test and symptom were induced in erdosteine and ambroxol treated group and two patients in ambroxol treated group drop-out for adverse reactions in symptom. 4) In the evaluation of final clinical efficacy, erdosteine improved more effectively patient's overall symptoms {very good effect (11/31), good effect (12/31), moderate effect (6/31), no effect (2/31), aggravation (0/31)} than ambroxol {very good effect (6/30), good effect (14/30), moderate effect (5/30), no effect (4/30), aggravation (2/30)}. And the probability of symptomatic improvement by erdosteine compared to ambroxol was 2.5 times. (p】