Abstract:
RATIONALE:The allergen inhalation challenge is used in clinical trials to test the efficacy of new treatments in attenuating the late-phase asthmatic response (LAR) and associated airway inflammation in subjects with allergic asthma. However, not all subjects with allergic asthma develop the LAR after allergen inhalation. Blood-based transcriptional biomarkers that can identify such individuals may help in subject recruitment for clinical trials as well as provide novel molecular insights. OBJECTIVES:To identify blood-based transcriptional biomarker panels that can predict an individual's response to allergen inhalation challenge. METHODS:We applied RNA sequencing to total RNA from whole blood (n = 36) collected before and after allergen challenge and generated both genome-guided and de novo datasets: genes, gene-isoforms (University of California, Santa Cruz, UCSC Genome Browser), Ensembl, and Trinity. Candidate biomarker panels were validated using the NanoString platform in an independent cohort of 33 subjects. MEASUREMENTS AND MAIN RESULTS:The Trinity biomarker panel consisting of known and novel biomarker transcripts had an area under the receiver operating characteristic curve of greater than 0.70 in both the discovery and validation cohorts. The Trinity biomarker panel was useful in predicting the response of subjects that elicited different responses (accuracy between 0.65 and 0.71) and subjects that elicit a dual response (accuracy between 0.70 and 0.75) upon repeated allergen inhalation challenges. CONCLUSIONS:Interestingly, the biomarker panel containing novel transcripts successfully validated compared with panels with known, well-characterized genes. These biomarker-blood tests may be used to identify subjects with asthma who develop the LAR, and may also represent members of novel molecular mechanisms that can be targeted for therapy.
journal_name
Am J Respir Crit Care Medauthors
Singh A,Shannon CP,Kim YW,Yang CX,Balshaw R,Cohen Freue GV,Gauvreau GM,FitzGerald JM,Boulet LP,O'Byrne PM,Tebbutt SJdoi
10.1164/rccm.201701-0110OCsubject
Has Abstractpub_date
2018-02-15 00:00:00pages
450-462issue
4eissn
1073-449Xissn
1535-4970journal_volume
197pub_type
杂志文章abstract::Although sleep-disordered breathing (SDB) has been shown to be very prevalent in the elderly, little has been done to examine differences between the elderly of different racial groups. It has been well documented that SDB often results in hypertension and that hypertension is more common in African-Americans than in ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520760
更新日期:1995-12-01 00:00:00
abstract::The expression of renin-angiotensin system components and the elevation of angiotensin-converting enzyme (ACE) in a number of fibrotic lung diseases suggests angiotensin II (AII) could play a role in the pathogenesis of pulmonary fibrosis. However, the effect of AII on lung fibroblasts has not previously been assessed...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.6.9907004
更新日期:2000-06-01 00:00:00
abstract::Nitric oxide (NO) may play a part in pulmonary vascular regulation and bronchomotor control and has been detected in exhaled air. We report the release of NO from airway epithelial cells and its regulation by cyclic adenosine monophosphate (cAMP). To directly measure NO release, a highly specific amperometric sensor f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.4.7551390
更新日期:1995-10-01 00:00:00
abstract:RATIONALE:Acute lung injury (ALI) that develops 6 hours after transfusion (TRALI) is the leading cause of transfusion-related mortality. Several transfusion characteristics have been postulated as risk factors for TRALI, but the evidence is limited to retrospective studies. OBJECTIVES:To compare patient and transfusio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200702-271OC
更新日期:2007-11-01 00:00:00
abstract::Disordered breathing during sleep is associated with acute, unfavorable effects on cardiovascular physiology, but few studies have examined its postulated association with cardiovascular disease (CVD). We examined the cross-sectional association between sleep- disordered breathing and self-reported CVD in 6,424 free-l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/ajrccm.163.1.2001008
更新日期:2001-01-01 00:00:00
abstract:RATIONALE:Despite increasing recognition of bone morphogenetic protein (BMP) signaling in tissue remodeling, the expression pattern of ligands and signaling pathways remain undefined in the asthmatic airway. OBJECTIVES:To determine expression of BMP ligands (BMP-2, BMP-4, and BMP-7) and type I and type II receptors (A...
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.200709-1376OC
更新日期:2008-05-15 00:00:00
abstract::Positive pressure ventilation with large VTs has been shown to cause release of cytokines, including macrophage inflammatory protein-2 (MIP-2), a functional equivalent of human interleukin-8. The mechanisms regulating ventilation-induced cytokine production are unclear. Based on our previous in vitro model of lung cel...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200305-660OC
更新日期:2004-02-15 00:00:00
abstract::Dysfunction of the muscles of ambulation contributes to exercise intolerance in chronic obstructive pulmonary disease (COPD). Men with COPD have high prevalence of low testosterone levels, which may contribute to muscle weakness. We determined effects of testosterone supplementation (100 mg of testosterone enanthate i...
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/rccm.200305-617OC
更新日期:2004-10-15 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::Obstructive sleep-disordered breathing is associated with cardiovascular disease in adults, and elevated C-reactive protein (CRP) has been proposed as a link between the two disorders. We hypothesized that children with sleep-disordered breathing have higher CRP values than do control subjects. CRP was measured in 39 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-928OC
更新日期:2005-02-01 00:00:00
abstract::Physiologic adaptations after an 8-wk endurance training program were examined in 13 patients with chronic obstructive pulmonary disease (COPD) (age, 64 +/- 4 [SD] yr; FEV1, 43 +/- 9% pred; PaO2, 72 +/- 8 mm Hg; and PaCO2, 36 +/- 2 mm Hg) and in eight healthy sedentary control subjects (61 +/- 4 yr). Both pre- and pos...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9804136
更新日期:1999-06-01 00:00:00
abstract:RATIONALE:Although intermittent, three-times-weekly therapy is recommended for the initial treatment of noncavitary nodular bronchiectatic Mycobacterium avium complex (MAC) lung disease, supporting data are limited. OBJECTIVES:To evaluate the clinical efficacy of intermittent therapy compared with daily therapy for no...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201408-1545OC
更新日期:2015-01-01 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:RATIONALE:Recent cohort studies in chronic obstructive pulmonary disease (COPD) have questioned the validity of previously reported associations between inhaled corticosteroids (ICS) and reductions in mortality and rehospitalization in observational studies. Using time-dependent versions of statistical survival models,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200502-210OC
更新日期:2005-08-15 00:00:00
abstract::We have investigated the efficacy of a clarithromycin-containing four-drug regimen for Mycobacterium avium complex (MAC) pulmonary disease in 46 patients without acquired immunodeficiency syndrome (AIDS). The patients were 14 males and 32 females with a mean age of 60.9 +/- 11.5 yr. Patients received 10 mg/kg/d of cla...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.160.3.9811086
更新日期:1999-09-01 00:00:00
abstract::To better understand strategies for recruiting and maintaining lung volume in acute lung injury, we examined relationships between steady-state lung volume and cumulative cyclic recruitment/derecruitment volume history and the quasi-static pressure-volume curve, in an animal saline lavage lung injury model. Small-volu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200305-614OC
更新日期:2004-04-15 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). OBJECTIVES:We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201403-0526OC
更新日期:2014-09-01 00:00:00
abstract::Characterization of chemokine expression patterns in virus-infected epithelial cells provides important clues to the pathophysiology of such infections. The aim of this study was to determine the chemokine response pattern of respiratory epithelium when infected with respiratory syncytial virus (RSV). Macrophage infla...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9805083
更新日期:1999-06-01 00:00:00
abstract::Impaired lung epithelial Na(+) channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the alphaENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9905064
更新日期:2000-04-01 00:00:00
abstract::We investigated whether cephalometric measurements, nocturnal indices of negative intrathoracic pressure, or the frequency of sleep-related breathing disorders were related to the level of effective continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA). We examined 22 OSA patients w...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.6.7767530
更新日期:1995-06-01 00:00:00
abstract::Retrospective studies have suggested that combination antibiotic therapy for severe bacteremic pneumococcal pneumonia may reduce mortality. We assessed this issue in a prospective, multicenter, international observational study of 844 adult patients with bacteremia due to Streptococcus pneumoniae. The effect of combin...
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
doi:10.1164/rccm.200311-1578OC
更新日期:2004-08-15 00:00:00
abstract::To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested wh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.3.9705034
更新日期:1998-03-01 00:00:00
abstract::Alkaline phosphatase (ALP) in lung lavage fluids is a marker of tissue damage and type II cell proliferation. Type II pneumocytes are extensively involved in fibrosis. The aim of our study was to verify whether local ALP activity can be held as a marker of fibrosis in chronic interstitial lung disorders. ALP was deter...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.1.9001320
更新日期:1997-01-01 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::To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.3.7663800
更新日期:1995-09-01 00:00:00
abstract::Lung transplantation with its attendant life-long immunosuppression contributes to bone loss and its sequelae, fractures and kyphosis, in patients with lung disease, many of whom already suffer from severe osteoporosis. Patients with cystic fibrosis (CF) are one of the most severely affected groups. We conducted a con...
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.162.3.2002051
更新日期:2000-09-01 00:00:00
abstract::Allergen inhalation challenge is associated with increases in eosinophil number and activation, and provides a useful model for investigating airway inflammation in asthma. Limited information, however, is available on the effect of allergen challenge on cytokines regulating eosinophil function. We investigated allerg...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.6.7767540
更新日期:1995-06-01 00:00:00
abstract:RATIONALE:The American Thoracic Society/European Respiratory Society International Consensus Classification panel identified the clinical entity idiopathic nonspecific interstitial pneumonia (NSIP) as a provisional diagnosis and recommended further study. OBJECTIVES:We hypothesized that idiopathic NSIP is an autoimmun...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200702-220OC
更新日期:2007-10-01 00:00:00
abstract:RATIONALE:An increasing number of persons, exposed to high altitude for leisure, sport, or work, may suffer from severe high-altitude illness. OBJECTIVES:To assess, in a large cohort of subjects, the association between physiological parameters and the risk of altitude illness and their discrimination ability in a ris...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201108-1396OC
更新日期:2012-01-15 00:00:00
abstract::To assess whether there is increased risk of tuberculous infection in children who traveled to or had a household visitor from a country having a high prevalence of tuberculosis, we conducted a case-control study. Children younger than 6 yr of age who had a tuberculin skin test read at public health clinics in areas o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.6.9804106
更新日期:1998-12-01 00:00:00