Abstract:
RATIONALE:Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) characterized by abnormal extracellular matrix (ECM) remodeling. We hypothesized that ECM remodeling might result in a plasma profile of proteins specific for IPF that could distinguish patients with IPF from other idiopathic ILDs. OBJECTIVES:To identify biomarkers that might assist in distinguishing IPF from non-IPF ILD. METHODS:We developed a panel of 35 ECM, ECM-related, and lung-specific analytes measured in plasma from 86 patients with IPF (derivation cohort) and in 63 patients with IPF (validation cohort). Comparison groups included patients with rheumatoid arthritis-associated ILD (RA-ILD; n = 33), patients with alternative idiopathic ILDs (a-ILD; n = 41), and healthy control subjects (n = 127). Univariable and multivariable logistic regression models identified biomarkers that differentiated patients with IPF from those with a-ILD. Both continuous and diagnostic threshold versions of biomarkers were considered; thresholds were chosen to maximize summed diagnostic sensitivity and specificity in univariate receiver-operating characteristic curve analysis. A diagnostic score was created from the most promising analytes. MEASUREMENTS AND MAIN RESULTS:Plasma surfactant protein (SP)-D > 31 ng/ml, matrix metalloproteinase (MMP)-7 > 1.75 ng/ml, and osteopontin > 6 ng/ml each significantly distinguished patients with IPF from patients with a-ILD, both individually and in a combined index. The odds ratio for IPF when at least one analyte in the index exceeded the threshold was 4.4 (95% confidence interval, 2.0-9.7; P = 0.0003). When at least two analytes were elevated, the odds ratio for IPF increased to 5.0 (95% confidence interval, 2.2-11.5; P = 0.0002). CONCLUSIONS:A biomarker index of SP-D, MMP-7, and osteopontin enhanced diagnostic accuracy in patients with IPF compared with those with non-IPF ILD. Our data suggest that this biomarker index may improve diagnostic confidence in IPF.
journal_name
Am J Respir Crit Care Medauthors
White ES,Xia M,Murray S,Dyal R,Flaherty CM,Flaherty KR,Moore BB,Cheng L,Doyle TJ,Villalba J,Dellaripa PF,Rosas IO,Kurtis JD,Martinez FJdoi
10.1164/rccm.201505-0862OCsubject
Has Abstractpub_date
2016-11-15 00:00:00pages
1242-1251issue
10eissn
1073-449Xissn
1535-4970journal_volume
194pub_type
杂志文章abstract:RATIONALE:It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea. OBJECTIVES:We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea. METH...
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.200711-1675OC
更新日期:2008-06-15 00:00:00
abstract:RATIONALE:S100A12 is overexpressed during inflammation and is a marker of inflammatory disease. Furthermore, it has been ascribed to the group of damage-associated molecular pattern molecules that promote inflammation. However, the exact role of human S100A12 during early steps of immune activation and sepsis is only p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201209-1602OC
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abstract::Cell death is intertwined with life in development, homeostasis, pathology, and aging. Until recently, apoptosis was the best known form of programmed cell death, whereas necrosis was for a long time considered accidental owing to physicochemical injury. However, identification of crucial signaling and execution molec...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201510-2106CI
更新日期:2016-08-15 00:00:00
abstract::Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on ventilation-perfusion (VA/Q) distributions were determined during methacholine-induced bronchoconstriction in nine mechanically ventilated pigs. Animals inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or aerosolized terbuta...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.1.7812540
更新日期:1995-01-01 00:00:00
abstract::An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disod...
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.156.5.9611088
更新日期:1997-11-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
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abstract:RATIONALE:The development of host-targeted, prophylactic, and therapeutic interventions against tuberculosis requires a better understanding of the immune mechanisms that determine the outcome of infection with Mycobacterium tuberculosis. OBJECTIVES:To identify T-cell-dependent mechanisms that are protective in tuberc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201509-1746OC
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abstract::We investigated 116 Italian atopic families (560 individuals) for linkage with 13 DNA markers on chromosome 12. All the subjects were phenotyped for asthma, total serum IgE, bronchial hyperresponsiveness, skin-prick positivity to common aeroallergens, and atopy. A relative location map of the markers was prepared from...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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abstract:UNLABELLED:Although local tissue activation of the endothelin (ET) system contributes to the development of pulmonary hypertension, the impact of isolated chronic plasma hyperendothelinemia on the pulmonary circulation is unknown. METHODS:Mini-osmotic pumps were implanted in rats to deliver ET-1 during 7 or 28 days. A...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.200403-340OC
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abstract::Background: This document provides clinical recommendations for the pharmacologic treatment of chronic obstructive pulmonary disease (COPD). It represents a collaborative effort on the part of a panel of expert COPD clinicians and researchers along with a team of methodologists under the guidance of the American Thora...
journal_title:American journal of respiratory and critical care medicine
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doi:10.1164/rccm.202003-0625ST
更新日期:2020-05-01 00:00:00
abstract::Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha released from alveolar macrophages (AM) in pulmonary tuberculosis (TB) are important in host defense against mycobacterial infection. Nitric oxide (NO) production is enhanced in AM of TB patients. We examined whether NO was implicated in (IL)-1beta and TNF-a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9902113
更新日期:2000-01-01 00:00:00
abstract::The clinical significance of minimal acute rejection (grade A1) in lung transplant recipients is unknown. We prospectively analyzed 1,159 transbronchial lung biopsies in 184 patients. Two hundred seventy-nine biopsies in 128 participants confirmed A1 histology at a mean postoperative day of 229 +/- 340. Sixty four of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2004-11-01 00:00:00
abstract:RATIONALE:Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. OBJECTIVES:To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respirator...
journal_title:American journal of respiratory and critical care medicine
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更新日期:2006-12-15 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/rccm.2112065
更新日期:2002-09-01 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.201711-2300OC
更新日期:2018-06-04 00:00:00
abstract::The inheritance of asthma, evident from its high family concordance, is not well understood. To investigate whether asthma may be inherited through a major gene with two alleles, segregation analyses were conducted in 3,369 individuals from 906 nuclear families enrolled, without selection, in a longitudinal study of r...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.1.8680670
更新日期:1996-07-01 00:00:00
abstract::A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies f...
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abstract::Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) ...
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abstract:RATIONALE:Characteristics of and survival estimates for recipients of lung retransplantation in the modern era are unknown. OBJECTIVES:To compare lung retransplant patients in the modern era with historical retransplant patients, to compare retransplant patients with initial transplant patients in the modern era, and ...
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更新日期:2010-06-15 00:00:00
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abstract::Preventing, treating, and promoting recovery from critical illness due to pulmonary disease are foundational goals of the critical care community and the National Heart, Lung, and Blood Institute. Decades of clinical research in acute respiratory distress syndrome, acute respiratory failure, pneumonia, and sepsis have...
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journal_title:American journal of respiratory and critical care medicine
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abstract::Neutrophil infiltration is a major feature in the pathogenesis of the common cold, and respiratory viral infection is the major cause of asthma exacerbations. The factors regulating the neutrophil influx are unknown. Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, which has been implicated in several infl...
journal_title:American journal of respiratory and critical care medicine
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更新日期:1997-04-01 00:00:00
abstract::In addition to its central role in hemostasis, thrombin may play a role in inflammation and remodeling. To investigate the contribution of thrombin to allergic airway inflammation in asthma, we used an enzymatic assay to determine thrombin activity in bronchoalveolar lavage fluid obtained from 19 subjects with atopic ...
journal_title:American journal of respiratory and critical care medicine
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更新日期:2004-02-01 00:00:00
abstract::Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries wit...
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