Abstract:
:Rationale: Diagnosis and monitoring of patients with pulmonary artery hypertension (PAH) is currently difficult.Objectives: We aimed to develop a noninvasive imaging modality for PAH that tracks the infiltration of macrophages into the pulmonary vasculature, using a positron emission tomography (PET) agent, 68Ga-2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) mannosylated human serum albumin (MSA), that targets the mannose receptor (MR).Methods: We induced PAH in rats by monocrotaline injection. Tissue analysis, echocardiography, and 68Ga-NOTA-MSA PET were performed weekly in rats after monocrotaline injection and in those treated with either sildenafil or macitentan. The translational potential of 68Ga-NOTA-MSA PET was explored in patients with PAH.Measurements and Main Results: Gene sets related to macrophages were significantly enriched on whole transcriptome sequencing of the lung tissue in PAH rats. Serial PET images of PAH rats demonstrated increasing uptake of 68Ga-NOTA-MSA in the lung by time that corresponded with the MR-positive macrophage recruitment observed in immunohistochemistry. In sildenafil- or macitentan-treated PAH rats, the infiltration of MR-positive macrophages by histology and the uptake of 68Ga-NOTA-MSA on PET was significantly lower than that of the PAH-only group. The pulmonary uptake of 68Ga-NOTA-MSA was significantly higher in patients with PAH than normal subjects (P = 0.009) or than those with pulmonary hypertension by left heart disease (P = 0.019) (n = 5 per group).Conclusions:68Ga-NOTA-MSA PET can help diagnose PAH and monitor the inflammatory status by imaging the degree of macrophage infiltration into the lung. These observations suggest that 68Ga-NOTA-MSA PET has the potential to be used as a novel noninvasive diagnostic and monitoring tool of PAH.
journal_name
Am J Respir Crit Care Medauthors
Park JB,Suh M,Park JY,Park JK,Kim YI,Kim H,Cho YS,Kang H,Kim K,Choi JH,Nam JW,Kim HK,Lee YS,Jeong JM,Kim YJ,Paeng JC,Lee SPdoi
10.1164/rccm.201903-0639OCsubject
Has Abstractpub_date
2020-01-01 00:00:00pages
95-106issue
1eissn
1073-449Xissn
1535-4970journal_volume
201pub_type
杂志文章abstract:RATIONALE:The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. OBJECTIVES:To determine the extent of lung disease in a geographically defined...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0069OC
更新日期:2009-07-15 00:00:00
abstract:RATIONALE:Improved ventilation strategies have been the mainstay for reducing mortality in acute respiratory distress syndrome. Their unique clinical effectiveness is, however, unmatched by our understanding of the underlying mechanobiology, and their impact on alveolar dynamics and gas exchange remains largely specula...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201505-0901OC
更新日期:2016-02-15 00:00:00
abstract::A continuously mixed series of microbial communities inhabits various points of the respiratory tract, with community composition determined by distance from colonization sources, colonization rates, and extinction rates. Ecology and evolution theory developed in the context of biogeography is relevant to clinical mic...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201312-2129PP
更新日期:2014-06-01 00:00:00
abstract::The cells and proteases that mediate cigarette smoke-induced emphysema are controversial, with evidence favoring either neutrophils and neutrophil-derived serine proteases or macrophages and macrophage-derived metalloproteases as the important effectors. We recently reported that both macrophage metalloelastase (MMP-1...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200212-1396OC
更新日期:2003-04-15 00:00:00
abstract::Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.153.2.8564100
更新日期:1996-02-01 00:00:00
abstract::Methodologies used to assess airway responsiveness (AR) in children administer the same dosage schedule to all children despite the great range in the size of subjects. The aim of this study was to examine the hypothesis that the level of AR is size dependent within same-age cohorts and between different ages. Among a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.2.7633710
更新日期:1995-08-01 00:00:00
abstract::Pleural disease both before and after organ transplantation has important implications. Pleural effusions are common in candidates for heart, liver, and kidney transplantation. A thoracentesis is not mandatory in these patients, but it should be performed if clinical or radiologic features suggest that the effusion is...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.153.3.8630560
更新日期:1996-03-01 00:00:00
abstract::Increased pharyngeal collapsibility and abnormal anatomic structures have been postulated to contribute to the pathophysiology of obstructive sleep apnea (OSA) syndrome. It is unclear whether the abnormal craniofacial and soft tissue features may affect the pharyngeal collapsibility and contribute to the apnea density...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.2.9810091
更新日期:2000-02-01 00:00:00
abstract::A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic pr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.2.7633740
更新日期:1995-08-01 00:00:00
abstract::It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200207-765OC
更新日期:2004-03-01 00:00:00
abstract:RATIONALE:Exacerbation of chronic obstructive pulmonary disease commonly causes hospitalization. The change in lung mechanics during exacerbation and its relationship to symptoms in spontaneously breathing individuals has not been described. OBJECTIVE:We hypothesized that changes in both airflow and lung volumes would...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200504-595OC
更新日期:2005-12-15 00:00:00
abstract::11beta-hydroxysteroid dehydrogenases (11beta-HSD) are responsible for the conversion of bioactive glucocorticoids to and from inactive metabolites. 11beta-HSD2 is generally considered a high-affinity inactivator of natural glucocorticoids, although its activity with synthetic compounds in vivo is unknown. Inhaled cort...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.7.2105003
更新日期:2002-04-01 00:00:00
abstract:RATIONALE:Fibroblast growth factor receptor-1alpha(IIIc) [FGF-R1alpha(IIIc)] regulates recovery of neonatal rat lung growth, after 95% oxygen-mediated growth arrest. Its role in normal postnatal alveologenesis is unknown. OBJECTIVE:To determine if FGF-R1alpha(IIIc) regulates normal postnatal alveologenesis. METHODS:T...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200511-1718OC
更新日期:2006-09-01 00:00:00
abstract::Large pleural effusions are typically associated with dyspnea and potential respiratory compromise. Experimental evidence suggests that with large effusions, increased intrapleural pressure may be transmitted to the pericardial space, resulting in impaired cardiac filling and reduced stroke volume. We report two cases...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.3_Pt_1.904
更新日期:1995-03-01 00:00:00
abstract::Most of the studies linking chronic obstructive pulmonary disease (COPD) with oxidative stress are in vitro, using invasive techniques, or measuring systemic oxidative stress. The aim of this study was to quantify oxidative stress in the lungs in patients with COPD and in healthy smokers, as reflected by 8-isoprostane...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.3.2001063
更新日期:2000-09-01 00:00:00
abstract:RATIONALE:Previous investigations have identified several potential predictors of outcomes from lung volume reduction surgery (LVRS). A concern regarding these studies has been their small sample size, which may limit generalizability. We therefore sought to examine radiographic and physiologic predictors of surgical o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200906-0911OC
更新日期:2010-03-01 00:00:00
abstract:RATIONALE:Although it is widely assumed that the incidence of childhood respiratory allergies to common aeroallergens is directly related to allergen exposure in early life, few longitudinal studies have investigated this issue, and available data are scarce and mainly limited to high-risk groups. OBJECTIVES:To assess...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.200607-916OC
更新日期:2007-09-01 00:00:00
abstract:RATIONALE:The relative contribution of body proportion and social exposures to ethnic differences in lung function has not previously been reported in the United Kingdom. OBJECTIVES:To examine ethnic differences in lung function in relation to anthropometry and social and psychosocial factors in early adolescence. ME...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200706-867OC
更新日期:2008-06-01 00:00:00
abstract::There is intriguing evidence suggesting pathophysiologic relationships among dyspnea, hyperventilation, and panic anxiety. The symptoms of panic attacks and pulmonary disease overlap, so that panic anxiety can reflect underlying cardiopulmonary disease and dyspnea can reflect an underlying anxiety disorder. The pathog...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.154.1.8680700
更新日期:1996-07-01 00:00:00
abstract::We developed clonal cell lines of human bronchial smooth muscle origin by retroviral transduction of temperature-sensitive simian virus 40 large tumor (T) antigen. These cells show increased growth potential at 33 degrees C, but on shift to the nonpermissive temperature (39 degrees C), they show diminished or arrested...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200307-964OC
更新日期:2004-03-15 00:00:00
abstract:RATIONALE:Asthma treatment might improve when inhaled steroids are titrated on airway inflammation. Fractional exhaled nitric oxide (FeNO0.05), a marker of eosinophilic airway inflammation, can be measured at home. OBJECTIVES:We assessed daily FeNO0.05 telemonitoring in the management of childhood asthma. METHODS:Chi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.200807-1010OC
更新日期:2009-01-15 00:00:00
abstract::The lobar and cephalocaudal distribution of aerated and nonaerated lung and of PEEP-induced alveolar recruitment is unknown in acute lung injury (ALI). Dimensions of the lungs and volumes of aerated and nonaerated parts of each pulmonary lobe were measured using a computerized tomographic quantitative analysis and com...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.5.9802003
更新日期:1998-11-01 00:00:00
abstract::The gas exchange threshold (GET) has been used an an index of anaerobic threshold because it can be measured noninvasively. GET is estimated from a breakpoint in breath by breath values of carbon dioxide uptake (Vco2) and oxygen uptake (Vo2) obtained during a progressive exercise test. Three methods of estimating GET ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.1.7812580
更新日期:1995-01-01 00:00:00
abstract::A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-256OC
更新日期:2002-10-01 00:00:00
abstract::The number of patients awaiting lung transplantation (LT) and waiting time for surgery is increasing. In Australia, LT rates are 4. 6/million population/yr, which despite low organ donation rates, are the highest published in the world. The Australian organ allocation system allows identification of marginal donors an...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.1.9811017
更新日期:1999-07-01 00:00:00
abstract::alpha-Tocopherol is a potent antioxidant that effectively protects biological membranes against oxidative injury through coordination with ascorbic acid. Because propofol has a phenolic structure similar to that of alpha-tocopherol, this intravenous anesthetic may also have similar antioxidant activity. To test this h...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.165.1.2010134
更新日期:2002-01-01 00:00:00
abstract::Rationale: The management of indeterminate pulmonary nodules (IPNs) remains challenging, resulting in invasive procedures and delays in diagnosis and treatment. Strategies to decrease the rate of unnecessary invasive procedures and optimize surveillance regimens are needed.Objectives: To develop and validate a deep le...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201903-0505OC
更新日期:2020-07-15 00:00:00
abstract::Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.supplement_2.2106070
更新日期:2001-11-15 00:00:00
abstract:RATIONALE:Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis. OBJECTIVES:To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colist...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.201312-2208OC
更新日期:2014-04-15 00:00:00
abstract::We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.4.9806114
更新日期:1999-04-01 00:00:00