Abstract:
RATIONALE:Observational studies link statin therapy with improved outcomes in patients with severe sepsis. OBJECTIVES:To test whether atorvastatin therapy affects biologic and clinical outcomes in critically ill patients with severe sepsis. METHODS:Phase II, multicenter, prospective, randomized, double-blind, placebo-controlled trial stratified by site and prior statin use. A cohort of 250 critically ill patients (123 statins, 127 placebo) with severe sepsis were administrated either atorvastatin (20 mg daily) or matched placebo. MEASUREMENTS AND MAIN RESULTS:There was no difference in IL-6 concentrations (primary end point) between the atorvastatin and placebo groups (P = 0.76) and no interaction between treatment group and time to suggest that the groups behaved differently over time (P = 0.26). Baseline plasma IL-6 was lower among previous statin users (129 [87-191] vs. 244 [187-317] pg/ml; P = 0.01). There was no difference in length of stay, change in Sequential Organ Failure Assessment scores or mortality at intensive care unit discharge, hospital discharge, 28- or 90-day (15% vs. 19%), or adverse effects between the two groups. Cholesterol was lower in patients treated with atorvastatin (2.4 [0.07] vs. 2.6 [0.06] mmol/L; P = 0.006). In the predefined group of 77 prior statin users, those randomized to placebo had a greater 28-day mortality (28% vs. 5%; P = 0.01) compared with those who received atorvastatin. The difference was not statistically significant at 90 days (28% vs. 11%; P = 0.06). CONCLUSIONS:Atorvastatin therapy in severe sepsis did not affect IL-6 levels. Prior statin use was associated with a lower baseline IL-6 concentration and continuation of atorvastatin in this cohort was associated with improved survival. Clinical trial registered with the Australian New Zealand Clinical Trials Registry (ACTRN 12607000028404).
journal_name
Am J Respir Crit Care Medauthors
Kruger P,Bailey M,Bellomo R,Cooper DJ,Harward M,Higgins A,Howe B,Jones D,Joyce C,Kostner K,McNeil J,Nichol A,Roberts MS,Syres G,Venkatesh B,ANZ-STATInS Investigators–ANZICS Clinical Trials Group.doi
10.1164/rccm.201209-1718OCsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
743-50issue
7eissn
1073-449Xissn
1535-4970pii
rccm.201209-1718OCjournal_volume
187pub_type
杂志文章,多中心研究,随机对照试验abstract::Although abnormalities of alveolar fibrin turnover have been reported to play a role in the development of idiopathic pulmonary fibrosis (IPF), the pathophysiological relevance remains unclear. We therefore investigated the localization of tissue factor (TF) and fibrin deposition in patients with IPF using immunohisto...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.2.9608094
更新日期:1997-08-01 00:00:00
abstract::Asthma and chronic bronchitis are inflammatory diseases with extracellular matrix (ECM) remodeling and collagen deposition. Collagen homeostasis is controlled by metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). We evaluated MMP and TIMP balance in induced sputum of 10 control, 31 untreate...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.6.9803014
更新日期:1998-12-01 00:00:00
abstract::The potential role of nitric oxide synthase-2 (NOS2) in acute lung injury (ALI) has gained increasing attention. This study evaluates the effects of hypoxia, an important feature of ALI, on NOS2 expression in a rat model of ALI caused by exposure to hypoxia and LPS. Exposure to hypoxia alone had no effect on the expre...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200209-1027OC
更新日期:2003-08-01 00:00:00
abstract::To investigate whether the magnitude of blood flow contributes to ventilator-induced lung injury, 14 sets of isolated rabbit lungs were randomized for perfusion at either 300 (Group A: n = 7) or 900 ml/ min (Group B: n = 7) while ventilated with 30 cm H2O peak static pressure. Control lungs (Group C: n = 7) were venti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.6.9612006
更新日期:1998-06-01 00:00:00
abstract::Vitamin D receptor (VDR) polymorphisms have been associated with several immune-related diseases, and VDR and vitamin D itself modulate T cell differentiation. VDR maps to chromosome 12q, near a region commonly linked to asthma. We evaluated VDR as part of a 12q positional candidate survey, and in response to observat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200404-447OC
更新日期:2004-11-15 00:00:00
abstract::The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 ...
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
abstract::Cryptogenic fibrosing alveolitis has been reported to be associated with an increased risk of lung cancer. However, it has recently become apparent that cigarette smoking may be a risk factor for cryptogenic fibrosing alveolitis as well as for lung cancer, and so may confound the association between these conditions. ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9906062
更新日期:2000-01-01 00:00:00
abstract::The place of surgical treatment in obstructive sleep apnea syndrome (OSAS) remains unclear. Uvulopalatopharyngoplasty (UPPP) has a response rate of 41% overall and only 5% when retrolingual narrowing is present. Thus, in cases with suspected hypopharyngeal collapse maxillofacial surgery has been proposed with improved...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.2.9904058
更新日期:2000-08-01 00:00:00
abstract:RATIONALE:Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. OBJECTIVES:We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. METHODS:Primary human airway epithelial cells grown at air-liquid int...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200801-136OC
更新日期:2008-12-15 00:00:00
abstract::The long-acting beta 2-agonist salmeterol has been suggested to have other pharmacologic activities, that is, antiinflammatory capacities, in addition to its bronchodilator properties. We investigated the protective effect of 50 micrograms salmeterol in a placebo-controlled study on house dust mite-induced early- and ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.150.5.7952550
更新日期:1994-11-01 00:00:00
abstract:RATIONALE:The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200504-525OC
更新日期:2005-11-15 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::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:RATIONALE:Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA. OBJECTIVES:To determine whether serum levels of TARC and MDC ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200508-1271OC
更新日期:2006-06-15 00:00:00
abstract:RATIONALE:Chronic obstructive pulmonary disease (COPD) is characterized by chronic airflow limitation caused by a combination of airways disease (bronchiolitis) and parenchymal destruction (emphysema), whose relative proportion varies from patient to patient. OBJECTIVES:To explore and contrast the molecular pathogenes...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201507-1311OC
更新日期:2016-06-01 00:00:00
abstract::The rise in childhood asthma prevalence suggests a role for environmental factors in the etiology of this evolving epidemic; however, genetics also influence the occurrence of asthma. Glutathione S-transferase (GST) M1 may play a role in asthma and wheezing occurrence among those exposed to tobacco smoke, as it functi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2112064
更新日期:2002-08-15 00:00:00
abstract:RATIONALE:New vaccines are urgently needed to protect the vulnerable from bacterial pneumonia. Clinical trials of pneumonia vaccines are slow and costly, requiring tens of thousands of patients. Studies of pneumococcal vaccine efficacy against colonization have been proposed as a novel method to down-select between vac...
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.201503-0542OC
更新日期:2015-10-01 00:00:00
abstract::A noninvasive method to characterize inflammation and infection in the airways of nonexpectorating children with cystic fibrosis (CF) is needed for clinical and research purposes. Accordingly, we performed sputum inductions by administering 3% saline to 11 healthy control children and 20 children with CF, composed of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.8.2104075
更新日期:2001-10-15 00:00:00
abstract:RATIONALE:Pulmonary infection in cystic fibrosis (CF) is polymicrobial and it is possible that anaerobic bacteria, not detected by routine aerobic culture methods, reside within infected anaerobic airway mucus. OBJECTIVES:To determine whether anaerobic bacteria are present in the sputum of patients with CF. METHODS:S...
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.200708-1151OC
更新日期:2008-05-01 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:Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. OBJECTIVES:To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically rele...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201504-0760OC
更新日期:2016-01-15 00:00:00
abstract::Guidelines, protocols, and checklists (together called "protocols") can be immensely helpful in the clinical arena. However, clinicians and health care systems relying on protocols must assess whether benefits are being accrued, whether such "benefits" are real, and whether harm can be detected. These concerns are imp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201502-0314CP
更新日期:2016-01-01 00:00:00
abstract::Experimental and epidemiological evidence supports the hypothesis that exposure to mycobacteria has the potential to suppress the development of asthma and/or atopy and there are reports in the Chinese medical literature of repeated vaccination with inactivated BCG being effective in the management of asthma. Forty-th...
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.163.6.2003050
更新日期:2001-05-01 00:00:00
abstract:RATIONALE:Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA. OBJECTIVES:We investigated whether there was a defect in the actions of the glucocorticoid re...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201402-0314OC
更新日期:2015-01-01 00:00:00
abstract::Fibrosing alveolitis may occur alone (CFA) or in association with systemic sclerosis (FASSc). FASSc was recently shown to have a prognostic advantage over CFA. Because interleukin-8 (IL-8) is likely to be a major determinant of neutrophil alveolitis, we evaluated IL-8 expression in patients with CFA and FASSc and comp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.5.7735620
更新日期:1995-05-01 00:00:00
abstract:BACKGROUND:Lung cancer screening (LCS) has the potential to reduce the risk of lung cancer death in healthy individuals, but the impact of coexisting chronic illnesses on LCS outcomes has not been well defined. Consideration of the complex relationship between baseline risk of lung cancer, treatment-related harms, and ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201805-0986ST
更新日期:2018-07-15 00:00:00
abstract::Exaggerated airway narrowing in response to bronchoconstricting stimuli is a characteristic feature of asthmatic subjects. It is unknown whether the site of airway narrowing differs in asthmatic subjects from that observed in normal subjects. Increased airway wall thickness has been suggested as a contributing cause f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.154.5.8912780
更新日期:1996-11-01 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::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::Leukotrienes have been implicated in the bronchoconstriction caused by indirect stimuli. In the present study we examined the effect of oral ABT-761, a novel 5-lipoxygenase (5-LO) inhibitor, on exercise- and adenosine (AMP)-induced bronchoconstriction in nine asthmatics. At the four 1-d, single-dose treatment periods,...
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.155.3.9117020
更新日期:1997-03-01 00:00:00