Abstract:
RATIONALE:Sarcoidosis is a granulomatous disease of unknown etiology, although M. tuberculosis may play a role in the pathogenesis. The traditional view holds that inflammation in sarcoidosis is compartmentalized to involved organs. OBJECTIVES:To determine whether whole blood gene expression signatures reflect inflammatory pathways in the lung in sarcoidosis and whether these signatures overlap with tuberculosis. METHODS:We analyzed transcriptomic data from blood and lung biopsies in sarcoidosis and compared these profiles with blood transcriptomic data from tuberculosis and other diseases. MEASUREMENTS AND MAIN RESULTS:Applying machine learning algorithms to blood gene expression data, we built a classifier that distinguished sarcoidosis from health in derivation and validation cohorts (92% sensitivity, 92% specificity). The most discriminative genes were confirmed by quantitative PCR and correlated with disease severity. Transcript profiles significantly induced in blood overlapped with those in lung biopsies and identified shared dominant inflammatory pathways (e.g., Type-I/II interferons). Sarcoidosis and tuberculosis shared more overlap in blood gene expression compared with other diseases using the 86-gene signature reported to be specific for tuberculosis and the sarcoidosis signature presented herein, although reapplication of machine learning algorithms could identify genes specific for sarcoidosis. CONCLUSIONS:These data indicate that blood transcriptome analysis provides a noninvasive method for identifying inflammatory pathways in sarcoidosis, that these pathways may be leveraged to complement more invasive procedures for diagnosis or assessment of disease severity, and that sarcoidosis and tuberculosis share overlap in gene regulation of specific inflammatory pathways.
journal_name
Am J Respir Crit Care Medauthors
Koth LL,Solberg OD,Peng JC,Bhakta NR,Nguyen CP,Woodruff PGdoi
10.1164/rccm.201106-1143OCsubject
Has Abstractpub_date
2011-11-15 00:00:00pages
1153-63issue
10eissn
1073-449Xissn
1535-4970pii
201106-1143OCjournal_volume
184pub_type
杂志文章abstract::Rationale: Hyperlactatemia in sepsis may derive from a prevalent impairment of oxygen supply/demand and/or oxygen use. Discriminating between these two mechanisms may be relevant for the early fluid resuscitation strategy.Objectives: To understand the relationship among central venous oxygen saturation (ScvO2), lactat...
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.201812-2342OC
更新日期:2019-09-01 00:00:00
abstract::A dysfunction of pathways that normally cause contraction or relaxation of airways has been proposed to explain heightened levels of responsiveness produced by various insults to the airway. For example, we previously reported (4) that infection of cotton rats with the human respiratory syncytial virus (HRSV) leads to...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.5.9705026
更新日期:1998-05-01 00:00:00
abstract::In order to determine the long-term sequelae of prune belly syndrome (PBS) and whether the absence of abdominal wall musculature impairs exercise performance we studied nine patients 6 to 31 yr of age with PBS. Conventional spirometry, lung volumes, DLCO, and respiratory muscle strength were measured. A progressive 1-...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.4.8616560
更新日期:1996-04-01 00:00:00
abstract::Many patients with acute asthma do not respond adequately to currently accepted therapy, including oxygen, beta-agonists, and corticosteroids. Leukotriene receptor antagonists such as montelukast have demonstrated efficacy in chronic asthma, but their efficacy in acute asthma is unknown. In this randomized, double-bli...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.200208-802OC
更新日期:2003-02-15 00:00:00
abstract:RATIONALE:There is a need to develop novel noninvasive imaging biomarkers that help to evaluate antiinflammatory asthma treatments. OBJECTIVES:To investigate whether the extent of the segmental lung edema measured noninvasively using turbo-inversion recovery-magnitude magnetic resonance imaging (TIRM MRI) corresponds ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
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更新日期:2014-03-15 00:00:00
abstract:RATIONALE:Transfusion of erythrocytes stored for prolonged periods is associated with increased mortality. Erythrocytes undergo hemolysis during storage and after transfusion. Plasma hemoglobin scavenges endogenous nitric oxide leading to systemic and pulmonary vasoconstriction. OBJECTIVES:We hypothesized that transfu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.201405-0850OC
更新日期:2014-10-01 00:00:00
abstract::In Balb/C mice, painting the skin with ovalbumin (OVA) over a period of 14 days resulted in sensitization of the animals. This was documented by the appearance of OVA-specific IgE and IgG1 antibodies and increased total serum IgE levels. In addition, in regional (inguinal) lymph nodes of sensitized animals, OVA-specif...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.1.8111600
更新日期:1994-01-01 00:00:00
abstract::Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of the epithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (approximately 120-140/cell) on the cell surface. The microvilli cont...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
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更新日期:2005-07-01 00:00:00
abstract::This study examines hemodialysis clearances of isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Seven chronic hemodialysis patients were studied. Six were given single oral doses (INH 300 mg, RIF 600 mg, PZA 1000 mg, and EMB 25 mg/kg) 2 h before hemodialysis (Cobe Centrysystem 3 hemodialysis ...
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更新日期:1999-05-01 00:00:00
abstract::Patients with severe chronic obstructive pulmonary disease (COPD) do not use the sternocleidomastoid muscles when breathing at rest, but have a greater than normal neural drive to the rib-cage inspiratory muscles, the abdominal muscles, and the diaphragm. Yet the increased activation of the abdominal muscles and diaph...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.2.9710116
更新日期:1998-08-01 00:00:00
abstract::Tumor-associated angiogenesis is important for tumor growth and metastasis. Interleukin (IL)-8 was recently reported to be an important angiogenic factor both in vitro and in vivo. In this study we evaluated, for the first time, IL-8 messenger RNA (mRNA) expression in non-small-cell lung cancer (NSCLC), using real-tim...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.5.2002108
更新日期:2000-11-01 00:00:00
abstract:RATIONALE:Although interferon (IFN)-gamma release assays are approved for the diagnosis of latent tuberculosis infection (LTBI), limited data exist regarding their performance in HIV infection. OBJECTIVES:To compare tuberculin skin test (TST) results to the commercial IFN-gamma release assay QuantiFERON-TB Gold In-Tub...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200608-1088OC
更新日期:2007-04-01 00:00:00
abstract::The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-l...
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
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更新日期:2004-06-01 00:00:00
abstract::Because interleukin 8 (IL-8) is a potent neutrophil chemotactic and activating cytokine, we investigated IL-8 production in relation to neutrophil migration and elastase release in the human lung during unilateral community-acquired pneumonia (CAP). In 17 patients, the local response in the involved lung was compared ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.1.8542140
更新日期:1996-01-01 00:00:00
abstract:RATIONALE:Clinical benefits of fixed-dose 100-mg subcutaneous (SC) mepolizumab in prednisone-dependent patients are modest when sputum eosinophilia is not adequately controlled. OBJECTIVES:This study compared treatment response of weight-adjusted intravenous (IV) reslizumab in patients previously treated with 100-mg S...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.201707-1323OC
更新日期:2018-01-01 00:00:00
abstract::In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the inju...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2005127
更新日期:2001-08-15 00:00:00
abstract:RATIONALE:North American occupational health programs that switched from the tuberculin skin test (TST) to IFN-γ release assays for latent tuberculosis screening are reporting challenges with interpretation of serial testing results in healthcare workers (HCWs). However, limited data exist on the reproducibility of ser...
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更新日期:2013-10-15 00:00:00
abstract:RATIONALE:chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by speci...
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更新日期:2016-02-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.6.8970350
更新日期:1996-12-01 00:00:00
abstract::Exhaled nitric oxide (eNO) is elevated in patients with inflammatory pulmonary diseases and it has attracted increasing interest as a simple, noninvasive marker of airway inflammation. Little is known, however, about factors that might affect eNO in healthy subjects. We measured eNO in 157 healthy 7- to 13-yr-old chil...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.1.9804134
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abstract:RATIONALE:The relationship between clinical phenotype of childhood primary ciliary dyskinesia (PCD) and ultrastructural defects and genotype is poorly defined. OBJECTIVES:To delineate clinical features of childhood PCD and their associations with ultrastructural defects and genotype. METHODS:A total of 118 participan...
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pub_type: 杂志文章,多中心研究
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更新日期:2015-02-01 00:00:00
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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
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201003-0406OC
更新日期:2011-02-15 00:00:00
abstract::Human T lymphotropic virus type I (HTLV-I) is the etiological agent of adult T cell leukemia, and reports suggest that several other clinical conditions are associated with HTLV-I infection, including myelopathy and inflammatory pulmonary diseases. However, the clinical entity of HTLV-I-associated lung disease remains...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1999-09-01 00:00:00
abstract::We evaluated positron emission tomographic imaging of pulmonary transgene expression, using an enhanced mutant herpes simplex virus-1 thymidine kinase as the reporter gene, in the lungs of normal rats. Sixteen rats were studied 3 days after an intratracheal administration of 5 x 10(9) to 1 x 10(11) viral particles of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1217OC
更新日期:2003-05-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.5.9154890
更新日期:1997-05-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200408-1046OC
更新日期:2005-02-01 00:00:00
abstract:RATIONALE:In clinical trials, patients with cystic fibrosis and a G551D mutation who received ivacaftor experienced improvements in pulmonary and nutritional outcomes. However, whether these improvements reflect a change in disease trajectory cannot be determined without longer-term analyses with an appropriate compara...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.201503-0578OC
更新日期:2015-10-01 00:00:00
abstract::The inflection points of the pressure-volume curve have been used for setting mechanical ventilation in patients with acute lung injury. However, the lung status at these points has never been specifically addressed. In 12 patients with early lung injury we traced both limbs of the pressure-volume curve by means of a ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200312-1644OC
更新日期:2004-11-15 00:00:00