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 SC mepolizumab. METHODS:Ten prednisone-dependent patients with asthma (sputum eosinophils >3% and blood eosinophils >300 cells/μl), who had previously received mepolizumab (100 mg SC dosed every 4 wk [Q4W]) for at least 1 year, received two infusions of placebo (Q4W) followed by four infusions of 3.0 mg/kg reslizumab Q4W in a single-blind, placebo-controlled sequential trial. Primary outcomes were reduction of eosinophils in sputum and blood. Additional outcomes included FEV1, asthma control questionnaire, eosinophil peroxidase, IL-5, sputum and blood innate lymphoid cells group 2, eosinophil progenitor cells, and autoimmune responses. MEASUREMENTS AND MAIN RESULTS:IV reslizumab attenuated sputum eosinophils by 91.2% (P = 0.002), blood eosinophil counts by 87.4% (P = 0.004), and sputum eosinophil peroxidase levels by 65.5% (P = 0.03) compared with placebo. Attenuation of both local and systemic eosinophilia was associated with statistically significant improvements in FEV1 (P = 0.004) and asthma control questionnaire five-question instrument scores (P = 0.006). Decrease in percent sputum eosinophil was greater with reslizumab (by 42.7%) compared with mepolizumab (by 5.0%) and this was associated with greater improvement in asthma control questionnaire (P = 0.01; analysis of covariance of Δ between before and after treatment, mepolizumab vs. reslizumab, adjusted for baseline prednisone). Changes in sputum IL-5 and anti-eosinophil peroxidase IgG after anti-IL-5 therapy were predictors of response. CONCLUSIONS:Weight-adjusted IV reslizumab was superior to fixed-dose SC mepolizumab in attenuating airway eosinophilia in prednisone-dependent patients with asthma, with associated improvement in asthma control. Clinical trial registered with www.clinicaltrials.gov (NCT 02559791).
journal_name
Am J Respir Crit Care Medauthors
Mukherjee M,Aleman Paramo F,Kjarsgaard M,Salter B,Nair G,LaVigne N,Radford K,Sehmi R,Nair Pdoi
10.1164/rccm.201707-1323OCsubject
Has Abstractpub_date
2018-01-01 00:00:00pages
38-46issue
1eissn
1073-449Xissn
1535-4970journal_volume
197pub_type
杂志文章abstract:RATIONALE:Although research supports a sleep-disordered breathing and atrial fibrillation association, prospective data examining sleep-disordered breathing predicting incident atrial fibrillation are lacking. OBJECTIVES:To investigate sleep-disordered breathing indices as predictors of incident atrial fibrillation. ...
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.201508-1523OC
更新日期:2016-04-01 00:00:00
abstract:RATIONALE:The incidence of influenza-associated acute respiratory failure is unknown. OBJECTIVES:To estimate the population-based incidence of influenza-associated acute respiratory failure hospitalizations. METHODS:This is a cohort study from January 2003 through March 2009 using hospitalization databases for Arizon...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201212-2341OC
更新日期:2013-09-15 00:00:00
abstract::To examine whether diffuse pleural thickening (DPT) causes impairment of pulmonary function independent of other manifestations of asbestos-related disease, we studied individuals selected from 1,150 men with occupational asbestos exposure who had undergone pulmonary function testing and computed tomographic (CT) scan...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.3.8810620
更新日期:1996-09-01 00:00:00
abstract::Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were sig...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.6.9711039
更新日期:1998-06-01 00:00:00
abstract::Arousal is believed to be needed for upper airway opening in obstructive hypopneas-apneas, without compelling evidence to support this notion. The association may be incidental. I studied the temporal relation between arousal and opening and impact of arousal on flow response at opening in 82 patients (apnea-hypopnea ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200307-1023OC
更新日期:2004-03-01 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::Hypersensitivity pneumonitis (HP) develops after inhalation of many different environmental antigens, causing variable clinical symptoms that often make diagnosis uncertain. The prevalence of HP is higher than recognized, especially its chronic form. Mechanisms of disease are still incompletely known. Strategies to im...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.200409-1205WS
更新日期:2005-04-01 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::Sensitive measures of lung function applicable to young subjects are needed to detect early cystic fibrosis (CF) lung disease. Forty children with CF aged 2 to 5 years and 37 age-matched healthy control subjects performed multiple-breath inert gas washout, plethysmography, and spirometry. Thirty children in each group...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200407-895OC
更新日期:2005-02-01 00:00:00
abstract:BACKGROUND:The use of biomass as a cooking fuel is commonplace in developing countries and has been associated with chronic bronchitis and obstructive airway disease. METHODS:A cross-sectional survey was done in the village of Solis, close to Mexico City. Lifelong nonsmoking women 38 yr of age or older (n=841) complet...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200503-479OC
更新日期:2006-10-15 00:00:00
abstract::Normoxic lung ischemia/reperfusion (I/R) leads to oxidative injury of the pulmonary tissue. We analyzed angiotensin-converting enzyme (ACE) in perfused rat lungs upon I/R in order to assess the endothelial injury produced. I/R led to a time-dependent increase in ACE activity in the perfusate, from 145+/-14 mU to 252+/...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.4.96-12116
更新日期:1997-10-01 00:00:00
abstract::REM-related oxygen desaturation occurs in advanced Duchenne muscular dystrophy (DMD) and might be an independent predictor of disease progression. We have followed 18 patients for 10 yr after an initial respiratory sleep study or until death or onset of nasal ventilation. We measured baseline spirometry, blood gas ten...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.1.9805055
更新日期:1999-07-01 00:00:00
abstract::The nasal antiinflammatory effects produced by maintenance treatment with topical steroids include reduced production of cytokines. The present study explored nasal mucosal effects induced during the first 9 h after a single dose of topical budesonide. Nine subjects with allergic rhinitis due to birch or timothy polle...
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.162.5.9910094
更新日期:2000-11-01 00:00:00
abstract:RATIONALE:Epithelial-mesenchymal transition (EMT) plays a key role in the development of chronic obstructive pulmonary disease (COPD) and lung cancer. OBJECTIVES:There are five major EMT regulatory genes (Snai1, Slug, Zeb1, Zeb2, and Twist1) involved in EMT. We hypothesized that germline variants in these genes may in...
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.201307-1355OC
更新日期:2014-01-15 00:00:00
abstract:RATIONALE:IL-9 is a pleiotropic cytokine that has multiple effects on structural as well as numerous hematopoietic cells, which are central to the pathogenesis of asthma. OBJECTIVES:The contribution of IL-9 to asthma pathogenesis has thus far been unclear, due to conflicting reports in the literature. These earlier st...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1462OC
更新日期:2011-04-01 00:00:00
abstract::This study investigated the clinico-pathologic correlation of tumor angiogenesis in non-small-cell lung cancers. Formalin-fixed, paraffin-embedded surgical specimens of 55 consecutive patients with primary non-small-cell lung cancers were examined. Included were 26 squamous cell carcinomas and 29 adenocarcinomas. Twen...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520790
更新日期:1995-12-01 00:00:00
abstract::A protective role for dietary antioxidants in asthma has been proposed. However, epidemiological evidence to implicate antioxidant vitamins is weak, and data on the role of flavonoid-rich foods and antioxidant trace elements are lacking. We carried out a population-based case-control study in South London, UK, to inve...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.10.2104061
更新日期:2001-11-15 00:00:00
abstract::The mechanisms of exertional dyspnea relief in response to supplemental oxygen (O2) in chronic airflow limitation (CAL) are not precisely known and are likely multifactorial. To explore factors contributing to the relief of dyspnea after oxygen administration, 11 patients with severe CAL (FEV1.0 = 39 +/- 3% predicted,...
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.155.2.9032190
更新日期:1997-02-01 00:00:00
abstract::The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing proc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564110
更新日期:1996-02-01 00:00:00
abstract::The failure of patients to adhere to physician-prescribed regimens, either pharmacologic or behavioral, has been well documented in medical literature. Poor adherence to asthma medication regimens has been repeatedly demonstrated in both children and adults, with rates of nonadherence commonly reported from 30 to 70%....
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm/149.2_Pt_2.S69
更新日期:1994-02-01 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::The virulence of Pseudomonas aeruginosa is partly controlled by the las quorum-sensing system. A rat model of acute pneumonia was used to investigate the pathophysiological impact of this system by comparing the virulence of the wild-type virulent laboratory strain PAO1 with that of its lasR-deleted mutant PAOR. In co...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200207-736BC
更新日期:2003-06-01 00:00:00
abstract:RATIONALE:Data on hemoptysis of unknown origin (i.e., "cryptogenic") are scarce and the outcome of patients affected is controversial. OBJECTIVES:To describe the clinical spectrum and course of patients with cryptogenic hemoptysis, as well as pathologic findings when surgery is performed. METHODS:A cohort of 81 patie...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1362OC
更新日期:2007-06-01 00:00:00
abstract:RATIONALE:The acute respiratory distress syndrome is a significant cause of morbidity and mortality in critically ill patients. Angiopoietin-1 (Ang-1), a ligand for the endothelial Tie2 receptor, is an endothelial survival and vascular stabilization factor that reduces endothelial permeability and inhibits leukocyte-en...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1370OC
更新日期:2007-05-15 00:00:00
abstract:RATIONALE:Few studies have examined associations between exposure to air pollution and childhood lung function after implementation of strict air quality regulations in the 1990s. OBJECTIVES:To assess traffic-related pollution exposure and childhood lung function. METHODS:We geocoded addresses for 614 mother-child pa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201506-1058OC
更新日期:2016-04-15 00:00:00
abstract::The last century experienced remarkable advances in the classification, diagnosis, and understanding of the pathogenesis of the interstitial lung diseases. Technological advances, particularly physiologic testing, lung imaging studies, bronchoalveolar lavage, surgical lung biopsy, and histopathologic assessment, impro...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.200503-483OE
更新日期:2005-08-01 00:00:00
abstract::The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-184OC
更新日期:2002-12-15 00:00:00
abstract::The appearance of portable chest radiographs (CXRs) may be affected by changes in ventilation, particularly when patients are mechanically ventilated. Synchronization of the CXR with the ventilatory cycle should limit the influence of respiratory variation on the appearance of the CXR. This study evaluates the effect ...
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.160.6.9902060
更新日期:1999-12-01 00:00:00
abstract::A major cause of morbidity and mortality following lung transplantation is posttransplant lymphoproliferative disease (PTLD). In a retrospective cohort analysis of pediatric patients, we evaluated the risk factors associated with PTLD in 128 first-time lung transplant recipients from 1990 to 1997. The greatest risk fa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9901013
更新日期:2000-04-01 00:00:00
abstract::Snoring and sleeping apnea are reportedly associated with morbidity. We used home monitoring (MESAM IV) to measure snoring and sleep apnea in 294 men aged 40 to 65 yr from the volunteer register of the Busselton (Australia) Health Survey. In this group, 81% snored for more than 10% of the night and 22% for more than h...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.5.7735600
更新日期:1995-05-01 00:00:00