Plasma C-Reactive Protein and Endothelin-1 Level in Patients with Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension

권용수,지수영,신홍준,김은영,윤병갑,반희정,오인재,김규식,김영철,임성철 대한의학회 2010 Journal of Korean medical science Vol.25 No.10

Pulmonary hypertension is a frequent complication of chronic obstructive pulmonary disease (COPD) and associated with a worse survival and increased risk of hospitalization for exacerbation of COPD. However, little information exists regarding the potential role of systemic inflammation in pulmonary hypertension of COPD. The purpose of the present study was to investigate the degree of C-reactive protein (CRP) and endothelin-1 (ET-1)levels in COPD patient with and without pulmonary hypertension. The levels of CRP and ET-1 were investigated in 58 COPD patient with pulmonary hypertension and 50 patients without pulmonary hypertension. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (Ppa) ≥35 mmHg assessed by Doppler echocardiography. Plasma CRP and ET-1 levels were significantly higher in patients with pulmonary hypertension than in patients without hypertension. There were significant positive correlations between the plasma ET-1 level and CRP level in the whole study groups. For COPD patients, systolic Ppa correlated significantly with plasma CRP levels and plasma ET-1 levels. These findings support a possibility that CRP and ET-1 correlate to pulmonary hypertension in COPD patients.

유지 혈액투석을 받는 말기신질환 환자의 폐고혈압

정창수 ( Chang Su Chun ),이영기 ( Young Ki Lee ),최종수 ( Jong Soo Choi ),이승민 ( Seung Min Lee ),송영림 ( Young Rim Song ),김수진 ( Soo Jin Min ),박태진 ( Tae Jin Park ),오지은 ( Ji Eun Oh ),서장원 ( Jang Won Seo ),윤종우 ( Jong 대한신장학회 2011 Kidney Research and Clinical Practice Vol.30 No.1

Purpose: Pulmonary hypertension can occur from diverse etiologies. It was reported that pulmonary hypertension also complicated dialysis patents, but the exact mechanisms were not determined. The aim of this study was to evaluate the prevalence and risk factors of pulmonary hypertension in maintenance hemodialysis patients. In addition, we studied the relationship between pulmonary hypertension and arteriovenous access. Methods: Fifty-nine chronic hemodialysis patients underwent clinical evaluation. Pulmonary artery pressure (PAP) was estimated by Doppler echocardiography. Pulmonary hypertension was defined as PAP ≥35 mmHg. Results: Mean PAP value of subjects was 39.3±13.2 mmHg. Pulmonary hypertension was found in 31 (53%) of patients receiving hemodialysis (49.0±10.6 mmHg; range 37 to 84 mmHg). Clinical and biochemical parameters did not differ significantly between patients with pulmonary hypertension and without pulmonary hypertension. In 19 patients, PAP was elevated from 27.8±10.2 mmHg to 41.8±11.9 mmHg (p<0.001) after onset of hemodialysis via arteriovenous fistula. And pulmonary hypertension developed in 12 of 15 patients with normal PAP after onset of hemodialysis treatment. Conclusion: The prevalence of pulmonary hypertension was high, and hemodialysis via arteriovenous access may be involved in the development of pulmonary hypertension.

Monocrotaline 유발성 폐고혈압증의 폐동맥 변화에 관한 전자현미경적 연구

김경수,이중달 한양대학교 의과대학 1995 한양의대 학술지 Vol.15 No.1

Pulmonary hypertension is reflected by histologic changes in the pulmonary arteries, namely small arteries and arterioles. Although arterial changes of pulmonary hypertension have been described in human lungs secondary to congenital heart disease of arterio-venous shunt, morphologic changes of pulmonary arteries in pulmonary hypertension were fragmentary and the pathogenesis remained unclear. To elucidate sequential changes of small arteries and arterioles and pathogenesis of the arterial changes in pulmonary hypertension, monocrotaline-induced pulmonary hypertension was produced in 63 Sprague-Dawley rats. Histologic and transmission electron microscopic studies of hypertensive pulmonary arteries from the experimental animals were carried out. Histologic changes in monocrotaline-induced pulmonary hypertension were mainly observed in the small arteries and arterioles. Early changes included vacuolization of the endothelial cells, edema, and fragmentation of the internal elastic lamina. As the early changes had subsided, the smooth muscle cell proliferation in the media was followed by increased thickness of the wall, which led to obliteration of their lumens. The degree of these histologic changes were not correlated with the dose of monocrotalin injected. On electron microscopic examination, the early changes consisted of endothelial cell injury, fragmentation of the internal elastic lamina and proliferation of smooth muscle cells in the media. Smooth muscle cell and fibroblast proliferation in the intima and media along with collagen and ground substance deposition was features of the late changes. In conclusion, monocrotaline-induced pulmonary hypertension was manifested as the early changes of endothelial cell injury of small arteries and arterioles followed by proliferation of smooth muscle cells and fibroblasts. This led to thickening of the arterial walls and obliteration of the lumens. The results indicated that monocrotaline was toxic to endothelial cells of the small arteries and arterioles of the lung, and that pathogenesis of monocrotaline-induced pulmonary hypertension appeared identical with those of essential hypertension.

Use of Inhaled Iloprost in an Infant With Bronchopulmonary Dysplasia and Pulmonary Artery Hypertension

황승경,오영철,김남수,박현경,염명걸 대한심장학회 2009 Korean Circulation Journal Vol.39 No.8

Pulmonary artery hypertension is a common cardiovascular complication in preterm infants with bronchopulmonary dysplasia which is associated with increased morbidity and mortality. Inhaled iloprost is used as a therapeutic option in pulmonary hypertension, especially in adults. There have been but a few reports on the use of iloprost for neonates and infants. We report the case of a 5 month-old-male infant who received neonatal intensive care for 4 months due to respiratory distress syndrome and prematurity, during which he developed bronchopulmonary dysplasia. Echocardiography showed severe pulmonary hypertension. The initial treatment included respiratory support with high frequency oscillatory ventilation (HFOV); however, his clinical condition did not improve. Inhaled iloprost with sildenafil, an oral phosphodiesterase-5 inhibitor, was thus used. With the administration of iloprost and sildenafil, his condition improved and he was weaned from oxygen. Our clinical experience suggests that iloprost is a promising therapy for pulmonary hypertension, especially when inhaled nitric oxide is unavailable. Pulmonary artery hypertension is a common cardiovascular complication in preterm infants with bronchopulmonary dysplasia which is associated with increased morbidity and mortality. Inhaled iloprost is used as a therapeutic option in pulmonary hypertension, especially in adults. There have been but a few reports on the use of iloprost for neonates and infants. We report the case of a 5 month-old-male infant who received neonatal intensive care for 4 months due to respiratory distress syndrome and prematurity, during which he developed bronchopulmonary dysplasia. Echocardiography showed severe pulmonary hypertension. The initial treatment included respiratory support with high frequency oscillatory ventilation (HFOV); however, his clinical condition did not improve. Inhaled iloprost with sildenafil, an oral phosphodiesterase-5 inhibitor, was thus used. With the administration of iloprost and sildenafil, his condition improved and he was weaned from oxygen. Our clinical experience suggests that iloprost is a promising therapy for pulmonary hypertension, especially when inhaled nitric oxide is unavailable.

Pulmonary Hypertension in Newborn Infants with Vein of Galen Malformation

( Woo Sun Song ),( Moon Yeon Oh ),( Jae Young Cho ),( Chae Young Kim ),( Dae Chul Suh ),( Euiseok Jung ),( Ellen Ai-rhan Kim ),( Ki-soo Kim ),( Byong Sop Lee ) 대한주산의학회 2019 Perinatology Vol.30 No.2

Objective: Vein of Galen malformation (VGM) is a rare cerebrovascular malformation. Children with VGM presenting in newborn period demonstrate various clinical courses from normal development to severe neurologic impairment or death. The aim of our study was to describe the characteristics of pulmonary hypertension and its treatment response in newborn infants with VGM. Methods: We retrospectively reviewed medical records of newborn infants with VGM who were antenatal diagnosed and treated with endovascular embolization in a single tertiary center. Clinical characteristics including echocardiographic data were described. Results: A total of six patients were diagnosed with VGM. Endovascular embolization was performed early postnatal days (median, 6.5 days) in four patients who required cardiorespiratory support. Echocardiography revealed pulmonary hypertension in the four cases and two of them received targeted therapy against pulmonary hypertension including inhaled nitric oxide and other pulmonary vasodilators. Incomplete occlusion of VGM failed to reverse the pulmonary hypertension. Mortality occurred in two patients with severe pulmonary hypertension in whom incomplete occlusion for VGM lesion. The cause of death was multi-organ failure secondary to right heart failure. Conclusion: Pulmonary hypertension was a common manifestation in newborn case with symptomatic VGM. The efficacy of early embolization and management for pulmonary hypertension in the newborn cases with persistent pulmonary hypertension of the newborn requires further large studies.

선천성 횡격막 탈장을 제외한 폐형성장애의 자연 경과와 예후 인자

김민수,최윤정,이승현,김우선,서동인,김민정 대한 소아알레르기 호흡기학회 2020 Allergy Asthma & Respiratory Disease Vol.8 No.4

Purpose: Pulmonary underdevelopment is one of the pulmonary causes of neonatal mortality, which is categorized into pulmonary agenesis, pulmonary aplasia, and pulmonary hypoplasia. Congenital diaphragmatic hernia is a well-known cause of pulmonary hypoplasia; however, further studies are needed for other etiologies. Patients with pulmonary underdevelopment show varying degrees of clinical severity. Most patients with pulmonary underdevelopment have respiratory distress at birth, while a few have only mild symptoms. Our study investigated the natural course and prognosis of pulmonary underdevelopment by analyzing multiple cases from a single tertiary medical center. Methods: A retrospective review was conducted on patients diagnosed with pulmonary hypoplasia and agenesis from January 2000 to August 2019. Cases were extracted from the clinical database of Seoul National University Children’s Hospital by searching for keywords related to pulmonary underdevelopment. Results: A total of 28 patients were identified. Four patients had pulmonary agenesis, and all were idiopathic. Twenty-four patients had evidence of pulmonary hypoplasia with diverse causes. The median age at diagnosis was 11.5 days (range, 1–240 days) and the mean gestational age was 35 weeks 2 days±3 weeks 6 days. Twenty patients received ventilator care and 11 had various degrees of pulmonary hypertension. The long-term survival rate was 50%. The median age of death among pulmonary hypoplasia patients were 11 days (range, 1–730 days). All patients without ventilator care survived. The incidence of ventilator care, pneumothorax, and pulmonary hypertension were significantly higher among patients who died. Conclusion: The prognosis of pulmonary underdevelopment depends on the severity of respiratory distress and pulmonary hypertension in earlier life. Patients with severe distress appear to have severe degree of pulmonary hypoplasia. Patients without ventilator support in the neonatal period survived without significant morbidities. .

Chronic Thromboembolic Pulmonary Hypertension: Endovascular Treatment

Chul-Min Ahn,Matsubara Hiromi 대한심장학회 2019 Korean Circulation Journal Vol.49 No.3

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare cause of pulmonary hypertension; less than 5% of pulmonary hypertension is caused by recurrent pulmonary thromboembolism (PTE). By definition, CTEPH happens within the first two years after symptomatic PTE; however, cases are often diagnosed without a history of acute PTE. Because of the poor functional status and chronicity of this disease, the classic and curative strategy of open pulmonary endarterectomy cannot be applied in some patients with lesions that involve the distal subsegmental pulmonary artery. Bridging therapy is needed for cases that are technically operable but have an unacceptable risk-benefit assessment or residual symptomatic pulmonary hypertension following surgical removal. Groups in Europe and Japan recently introduced balloon pulmonary angioplasty or percutaneous transluminal pulmonary angioplasty, which has led to significant improvement in functional and hemodynamic parameters in patients with CTEPH. This article introduces recent updates in patient selection and interventional procedures for this chronic and devastating disease.

Isolated Pulmonary Arterial Hypertension-Janus’ Faces of Hyperthyroidism

강버들,조덕규,변기현,은영민,조윤형 대한심장학회 2009 Korean Circulation Journal Vol.39 No.4

We describe a 54-year-old woman with isolated pulmonary arterial hypertension accompanied by hyperthyroidism due to Graves’ disease. Her pulmonary artery hypertension resolved spontaneously after restoration of euthyroidism. This case suggests that hyperthyroidism should be considered a reversible cause of pulmonary arterial hypertension. We describe a 54-year-old woman with isolated pulmonary arterial hypertension accompanied by hyperthyroidism due to Graves’ disease. Her pulmonary artery hypertension resolved spontaneously after restoration of euthyroidism. This case suggests that hyperthyroidism should be considered a reversible cause of pulmonary arterial hypertension.

결핵성 파괴폐에 의한 폐동맥 고혈압 환자에서 발견된 근위부 폐동맥 혈전증

이지은 ( Ji Eun Lee ),김정현 ( Jung Hyun Kim ),강민경 ( Min Kyoung Kang ),박현정 ( Hyun Jeong Park ),이지현 ( Ji Hyun Lee ),김은경 ( Eun Kyung Kim ),이영경 ( Young Kyung Lee ),정혜철 ( Hye Cheol Jeong ) 대한결핵 및 호흡기학회 2008 Tuberculosis and Respiratory Diseases Vol.64 No.1

Pulmonary arterial thrombosis develops during hypercoagulable states, intra-arterial tumorous conditions, and congenital heart disease accompanied by pulmonary hypertension. Thrombosis in the main pulmonary arterial stump after pneumonectomy can also occur. Herein, we report a very rare case of pulmonary arterial thrombosis in a patient with pulmonary hypertension and a lung destroyed by tuberculosis. He presented with aggravated dyspnea without fever or purulent sputum. His chest computerized tomography scan showed left main pulmonary arterial thrombosis as a convex shape, with the ipsilateral distal arteries and arterioles showing parenchymal destruction. After excluding pulmonary thromboembolism and hypercoagulable disorders, we diagnosed pulmonary arterial thrombosis and treated him with an anticoagulant. (Tuberc Respir Dis 2008;64:28-32)

SMAD1 Deficiency in Either Endothelial or Smooth Muscle Cells Can Predispose Mice to Pulmonary Hypertension

Han, Chul,Hong, Kwon-Ho,Kim, Yong Hwan,Kim, Mi-Jung,Song, Cheol,Kim, Myung Joon,Kim, Seong-Jin,Raizada, Mohan K.,Oh, S. Paul American Heart Association, Inc. 2013 Hypertension Vol.61 No.5

<P>A deficiency in bone morphogenetic protein receptor type 2 (BMPR2) signaling is a central contributor in the pathogenesis of pulmonary arterial hypertension (PAH). We have recently shown that endothelial-specific <I>Bmpr2</I> deletion by a novel L1Cre line resulted in pulmonary hypertension. SMAD1 is one of the canonical signal transducers of the BMPR2 pathway, and its reduced activity has been shown to be associated with PAH. To determine whether SMAD1 is an important downstream mediator of BMPR2 signaling in the pathogenesis of PAH, we analyzed pulmonary hypertension phenotypes in <I>Smad1</I>-conditional knockout mice by deleting the <I>Smad1</I> gene either in endothelial cells or in smooth muscle cells using L1Cre or <I>Tagln</I>-Cre mouse lines, respectively. A significant number of the L1Cre(+);<I>Smad1</I> (14/35) and <I>Tagln</I>-Cre(+);<I>Smad1</I> (4/33) mutant mice showed elevated pulmonary pressure, right ventricular hypertrophy, and a thickening of pulmonary arterioles. A pulmonary endothelial cell line in which the <I>Bmpr2</I> gene deletion can be induced by 4-hydroxy tamoxifen was established. SMAD1 phosphorylation in <I>Bmpr2</I>-deficient cells was markedly reduced by BMP4 but unaffected by BMP7. The sensitivity of SMAD2 phosphorylation by transforming growth factor-β1 was enhanced in the <I>Bmpr2</I>-deficient cells, and the inhibitory effect of transforming growth factor-β1–mediated SMAD2 phosphorylation by BMP4 was impaired in the <I>Bmpr2</I>-deficient cells. Furthermore, transcript levels of several known transforming growth factor-β downstream genes implicated in pulmonary hypertension were elevated in the <I>Bmpr2</I>-deficient cells. Taken together, these data suggest that SMAD1 is a critical mediator of BMPR2 signaling pertinent to PAH, and that an impaired balance between BMP4 and transforming growth factor-β1 may account for the pathogenesis of PAH.</P>