Abstract:
RATIONALE:IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. OBJECTIVES:To evaluate efficacy and safety of AMG 317 in patients with moderate to severe asthma. METHODS:In this phase 2, randomized, double-blind, placebo-controlled study, patients received weekly subcutaneous injections of placebo or AMG 317 (75-300 mg) for 12 weeks, followed by a 4-week follow-up period. The primary endpoint was change from baseline at Week 12 in Asthma Control Questionnaire (ACQ) symptom score. MEASUREMENTS AND MAIN RESULTS:Mean ACQ change (SE) was -0.49 (0.09) in placebo (n = 74), and -0.43 (0.11), -0.58 (0.12), and -0.70 (0.09) in the AMG 317 75 mg (n = 73), 150 mg (n = 73), and 300 mg (n = 74) groups, respectively (treatment effect P = 0.25). No statistically significant differences were observed in the secondary endpoints. Numerical decreases in number of and time to exacerbations were noted in patients receiving AMG 317 150 mg and 300 mg. Preplanned analyses by tertile of baseline ACQ revealed that patients with higher baseline ACQ scores (>or=2.86) were more likely to respond to AMG 317. Serious adverse events were reported in three patients, each noted as not related to study drug. CONCLUSIONS:AMG 317 did not demonstrate clinical efficacy across the overall group of patients. Clinically significant improvements were observed in several outcome measures in patients with higher baseline ACQ scores. AMG 317 was safe and well tolerated in this study population. Clinical trial registered with www.clinicaltrials.gov (NCT 00436670).
journal_name
Am J Respir Crit Care Medauthors
Corren J,Busse W,Meltzer EO,Mansfield L,Bensch G,Fahrenholz J,Wenzel SE,Chon Y,Dunn M,Weng HH,Lin SLdoi
10.1164/rccm.200909-1448OCsubject
Has Abstractpub_date
2010-04-15 00:00:00pages
788-96issue
8eissn
1073-449Xissn
1535-4970pii
200909-1448OCjournal_volume
181pub_type
杂志文章,随机对照试验abstract:RATIONALE:The relation between birth weight and respiratory symptoms and asthma in children remains unclear. Previous studies focused on a relation at separate ages. A longitudinal analysis may lead to a better understanding. OBJECTIVES:To estimate the effect of birth weight on the development and course of respirator...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200610-1441OC
更新日期:2007-05-15 00:00:00
abstract:RATIONALE:Implementation of intervention strategies to prevent lung damage in early cystic fibrosis (CF) requires objective outcome measures that capture and track lung disease. OBJECTIVES:To define the utility of the Lung Clearance Index (LCI), measured by multiple breath washout, as a means to track disease progress...
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.201610-2158OC
更新日期:2017-05-01 00:00:00
abstract::The stimuli controlling pharyngeal dilator muscles are poorly defined. Local mechanoreceptors are a leading possibility. To address this, we assessed the relationship between two dilator muscle electromyograms (EMGs, i.e., genioglossus [GG-an inspiratory phasic muscle], tensor palatini [TP-a tonically active muscle]) ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.3.9912067
更新日期:2000-09-01 00:00:00
abstract:RATIONALE:MicroRNAs (miRNAs) destabilize mRNA transcripts and inhibit protein translation. miR-145 is of particular interest in cystic fibrosis (CF) as it has a direct binding site in the 3'-untranslated region of CFTR (cystic fibrosis transmembrane conductance regulator) and is upregulated by the CF genetic modifier T...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201704-0732OC
更新日期:2018-03-01 00:00:00
abstract:RATIONALE:The around-the-clock presence of an in-house attending critical care physician (24/7 coverage) is purported to be associated with improved outcomes among high-risk children with critical illness. OBJECTIVES:To evaluate the association of 24/7 in-house coverage with outcomes in children with critical illness....
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.201512-2456OC
更新日期:2016-12-15 00:00:00
abstract:RATIONALE:Phthalates are used widely in consumer products. Exposure to several phthalates has been associated with respiratory symptoms and decreased lung function. Associations between children's phthalate exposures and fractional exhaled nitric oxide (Fe(NO)), a biomarker of airway inflammation, have not been examine...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201203-0398OC
更新日期:2012-11-01 00:00:00
abstract::When dyspnea must be assessed clinically, there are three methods of assessment: the measurement of dyspnea with activities of daily living using clinical dyspnea ratings such as the modified Medical Research Council (MRC), the Baseline Dyspnea Index (BDI), and the Oxygen Cost Diagram (OCD); the measurement of dyspnea...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.4.9802091
更新日期:1998-10-01 00:00:00
abstract:RATIONALE:Our understanding of how airway remodeling affects regional airway elastic properties is limited due to technical difficulties in quantitatively measuring dynamic, in vivo airway dimensions. Such knowledge could help elucidate mechanisms of excessive airway narrowing. OBJECTIVES:To use anatomical optical coh...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0178OC
更新日期:2011-03-01 00:00:00
abstract::We review recent advances in the use of corticosteroids (CS) in pediatric lung disease. CS are frequently used, systemically or by inhalation. Their mechanisms of action in pulmonary diseases are ill defined. CS exert direct inhibitory effects on many inflammatory cells through genomic mechanisms. There is a time lag ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201107-1174CI
更新日期:2012-01-01 00:00:00
abstract:RATIONALE:Statin use has been linked to improved lung health in asthma and chronic obstructive pulmonary disease. We hypothesize that statins inhibit allergic airway inflammation and reduce airway hyperreactivity via a mevalonate-dependent mechanism. OBJECTIVES:To determine whether simvastatin attenuates airway inflam...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0018OC
更新日期:2009-10-15 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::The bactericidal activities of several once-weekly rifapentine (P)-containing combination regimens against Mycobacterium tuberculosis, and their ability to prevent the selection of rifampin (R)-resistant mutants, were compared with those of the standard six-times-weekly regimen consisting of R, isoniazid (H), and pyra...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.5.9709072
更新日期:1998-05-01 00:00:00
abstract::The aim of this study was to assess the influence of preservation solution type and extra- or intracellular composition on the occurrence of early graft dysfunction after clinical lung transplantation. For 170 patients who underwent a single (n = 124) or bilateral (n = 46) lung transplantation in two centers in Paris ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.7.2012135
更新日期:2001-10-01 00:00:00
abstract::Although overproduction of proinflammatory 5-lipoxygenase (5-LO)-derived leukotrienes (LTs) has been demonstrated in the lungs of patients with pulmonary fibrosis, their causal involvement in this condition has not been established. Bleomycin-induced pulmonary fibrosis was studied in mice rendered LT deficient by knoc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.2.2104050
更新日期:2002-01-15 00:00:00
abstract::To compare the effectiveness of information delivered to family members of critically ill patients by junior and senior physicians, we performed a prospective randomized multicenter trial in 11 French intensive care units. Patients (n = 220) were allocated at random to having their family members receive information b...
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.200305-645OC
更新日期:2004-02-15 00:00:00
abstract:RATIONALE:The activated leukocyte cell adhesion molecule (ALCAM) is a cluster of differentiation 6 ligand that is important for stabilizing the immunological synapse and inducing T-cell activation and proliferation. OBJECTIVES:In this study, we investigated the role of ALCAM in the development of inflammation in aller...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201703-0532OC
更新日期:2018-04-15 00:00:00
abstract::Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0167CR
更新日期:2010-08-15 00:00:00
abstract::Studies of the hemodynamic effects of nasal continuous positive airway pressure (n-CPAP) in normal subjects have had conflicting results. The largest study (n = 19) found no effect of up to 15 cm H2O on heart rate (HR), cardiac stroke volume (SV), or cardiac index. We hypothesized that n-CPAP, by increasing intrathora...
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.149.6.8004320
更新日期:1994-06-01 00:00:00
abstract:RATIONALE:Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES:To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHOD...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200407-914OC
更新日期:2005-06-01 00:00:00
abstract:RATIONALE:5-Hydroxytryptamine (5-HT) is involved in the pathogenesis of allergic airway inflammation (AAI). It is unclear, however, how 5-HT contributes to AAI and whether this depends on tryptophan hydroxylase (TPH) 1, the critical enzyme for peripheral 5-HT synthesis. OBJECTIVES:To elucidate the role of TPH1 and the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201208-1440OC
更新日期:2013-03-01 00:00:00
abstract::The role of nitric oxide (NO) in the host-defense against human tuberculosis (TB) is controversial. Although experimental evidence indicates that NO may play an important role in controlling TB, its expression in human tuberculous lungs has not been systematically characterized. We therefore investigated the expressio...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2201023
更新日期:2002-07-15 00:00:00
abstract::From an Aspergillus fumigatus complementary deoxyribonucleic acid (cDNA) library displayed on phage surface, an allergen formally termed rAsp f 3 was cloned. The open-reading frame of the cloned gene for the allergen encodes a protein of 168 amino acids with a predicted molecular mass of 18.5 kD, showing 36% identity ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.6.9702087
更新日期:1997-12-01 00:00:00
abstract::The frequency and determinants of exogenous reinfection and of endogenous reactivation of tuberculosis in patients previously treated are poorly understood. In Gran Canaria Island, Spain, between 1991 and 1996, 962 tuberculosis cases were confirmed by culture. Drug susceptibility testing was performed on available bac...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.3.2003070
更新日期:2001-03-01 00:00:00
abstract::Long-term effects of high doses of inhaled corticosteroids (ICS) on bone density and metabolism are still uncertain. Fifty-one patients (37 male, 14 female) using beclomethasone or budesonide at a daily dose > 800 microgram/d (high-dose group [Group HD] mean: 983 microgram/d [prescribed dose x estimated compliance]) o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.3.9802096
更新日期:1999-03-01 00:00:00
abstract:RATIONALE:In San Francisco, 70% of the tuberculosis cases occur among foreign-born persons, mainly from China, the Philippines, and Mexico. We postulate that there are differences in the characteristics and risk factors for tuberculosis among these populations. OBJECTIVES:To determine the clinical, epidemiological and...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2239OC
更新日期:2013-05-01 00:00:00
abstract::We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day) followed b...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200208-960OC
更新日期:2004-04-01 00:00:00
abstract:RATIONALE:Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. OBJECTIVE:To perform a comprehensive analysis of the early and la...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200506-927OC
更新日期:2006-01-15 00:00:00
abstract:BACKGROUND:The relative roles of mucus plugs and emphysema in mechanisms of airflow limitation and hypoxemia in smokers with chronic obstructive pulmonary disease (COPD) are uncertain. METHODS:We analyzed computed tomography (CT) lung images and lung function in participants in the Subpopulations and Intermediate Outc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202006-2248OC
更新日期:2020-11-12 00:00:00
abstract:RATIONALE:There is growing evidence that resident cells, such as fibroblasts and epithelial cells, can drive the persistent accumulation of dendritic cells (DCs) in chronically inflamed tissue, leading to the organization and the maintenance of ectopic lymphoid aggregates. This phenomenon, occurring through a chemokine...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1347OC
更新日期:2007-11-15 00:00:00
abstract::Premature lungs are highly susceptible to lung injuries, leading to bronchopulmonary dysplasia (BPD). Keratinocyte growth factor (KGF) is produced by the developing lung and may reduce the risk of BPD by preventing injury to the lung epithelium and enhancing its repair. To determine whether KGF concentrations in the a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200112-134BC
更新日期:2002-05-15 00:00:00