Abstract:
RATIONALE:HIV-tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an immunopathological reaction to mycobacterial antigens induced by antiretroviral therapy. Prednisone reduces morbidity in TB-IRIS, but the mechanisms are unclear. OBJECTIVES:To determine the effect of prednisone on the inflammatory response in TB-IRIS (antigen-specific effector T cells, cytokines, and chemokines). METHODS:Blood was taken from participants in a randomized placebo-controlled trial of prednisone for TB-IRIS, at 0, 2, and 4 weeks. Participants received prednisone at a dosage of 1.5 mg/kg/day for 2 weeks followed by 0.75 mg/kg/day for 2 weeks, or placebo at identical dosages. MEASUREMENTS AND MAIN RESULTS:Analyses included IFN-γ enzyme-linked immunospot (ELISPOT), reverse transcription-polymerase chain reaction on peripheral blood mononuclear cells after restimulation with heat-killed Mycobacterium tuberculosis, Luminex multiplex cytokine analysis of corresponding tissue culture supernatants, and Luminex multiplex cytokine analysis of serum. Fifty-eight participants with TB-IRIS (31 receiving prednisone, 27 receiving placebo) were included. In serum, significant decreases in IL-6, IL-10, IL-12 p40, tumor necrosis factor-α, IFN-γ, and IFN-γ-induced protein-10 concentrations during prednisone, but not placebo, treatment were observed. No differences in ELISPOT responses comparing prednisone and placebo groups were shown in response to ESAT-6 (early secreted antigen target-6), Acr1, Acr2, 38-kD antigen, or heat-killed H37Rv M. tuberculosis. Purified protein derivative ELISPOT responses increased over 4 weeks in the prednisone group and decreased in the placebo group (P = 0.007). CONCLUSIONS:The beneficial effects of prednisone in TB-IRIS appear to be mediated via suppression of predominantly proinflammatory cytokine responses of innate immune origin, not via a reduction of the numbers of antigen-specific T cells in peripheral blood.
journal_name
Am J Respir Crit Care Medauthors
Meintjes G,Skolimowska KH,Wilkinson KA,Matthews K,Tadokera R,Conesa-Botella A,Seldon R,Rangaka MX,Rebe K,Pepper DJ,Morroni C,Colebunders R,Maartens G,Wilkinson RJdoi
10.1164/rccm.201201-0094OCsubject
Has Abstractpub_date
2012-08-15 00:00:00pages
369-77issue
4eissn
1073-449Xissn
1535-4970pii
rccm.201201-0094OCjournal_volume
186pub_type
杂志文章,随机对照试验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::Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2109012
更新日期:2002-06-01 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 promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. OBJECTIVES:To determine the extent of lung disease in a geographically defined...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0069OC
更新日期:2009-07-15 00:00:00
abstract::Cigarette smoking causes the development of chronic bronchitis and chronic obstructive pulmonary disease. We hypothesized that exposure to cigarette smoke might initiate release of inflammatory mediators by bronchial epithelial cells. To evaluate this, the effect of cigarette smoke extract (CSE) on IL-8 release from c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.5.9154890
更新日期:1997-05-01 00:00:00
abstract::Lymphangioleiomyomatosis (LAM), a disease that occurs primarily in women, is characterized by cystic lung lesions causing respiratory failure, which may require lung transplantation. Lung diffusion (DLCO) and/or FEV1 are decreased, but frequently not in parallel with each other. Because cardiopulmonary exercise testin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200206-593OC
更新日期:2003-12-15 00:00:00
abstract::Pulmonary hypertension associated with congestive heart failure carries a risk of right ventricular failure after cardiac transplantation. Few data, however, are available on the hemodynamic behavior of the pulmonary circulation in these patients. We therefore studied mean pulmonary artery pressure minus left atrial p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.4.8143050
更新日期:1994-04-01 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: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
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doi:10.1164/rccm.200502-210OC
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201501-0116OC
更新日期:2015-07-01 00:00:00
abstract::The nasal mucosal is the first site of contact with inhaled antigens. However, the nature of local immune responses and the role of nasal-associated lymphoid tissue (NALT) in those responses have rarely been studied. To characterize the cells involved in mucosally derived immune responses, NALT and Peyer's patch (PP) ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.4.97-03017
更新日期:1997-10-01 00:00:00
abstract:RATIONALE:Small studies have suggested that inhaled corticosteroids can suppress systemic inflammation in chronic obstructive pulmonary disease (COPD). OBJECTIVES:To determine the effect of inhaled corticosteroids with or without long-acting beta(2)-adrenergic agonist on systemic biomarkers of inflammation. METHODS:W...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1164/rccm.200709-1356OC
更新日期:2008-06-01 00:00:00
abstract::The inflammatory events in the airways at the time of acute respiratory failure from acute severe asthma are poorly understood. To determine the patterns of cellular inflammation in the airways in acute severe asthma, we analyzed tracheal aspirates collected within 12 h of intubation from patients intubated emergently...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9812061
更新日期:2000-04-01 00:00:00
abstract::Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year m...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201909-1771OC
更新日期:2020-02-15 00:00:00
abstract::It is controversial whether obstructive sleep apnea (OSA) causes pulmonary hypertension (PH) in the absence of hypoxemic lung disease. To investigate this further we measured awake pulmonary hemodynamics, pulmonary gas exchange, and small airways function in 32 patients with OSA (apnea- hypopnea index, mean +/- SE, 46...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.5.9805086
更新日期:1999-05-01 00:00:00
abstract:RATIONALE:S. aureus is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the US. While modes of acquisition and genetic adaptation have been described for Pseudomonas aeruginosa, resulting in improved diagnosis and treatment, these features remain more poorly defined for S. aureus...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202003-0735OC
更新日期:2020-12-09 00:00:00
abstract::Transforming growth factor-beta1 (TGF-beta1) is a growth factor that is implicated in fibrosis of many organs. The purpose of this study was to determine the sequential levels of TGF-beta1 in the pleural fluid of rabbits that had undergone empyema induction, as fibrosis of the pleural space develops. Thirty-seven rabb...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2202043
更新日期:2003-09-15 00:00:00
abstract::Most data about the course of occupational asthma after removal from exposure are based upon the longitudinal assessment of employees exposed to substances inducing late asthmatic reactions in bronchial provocation tests. It was the aim of this study to describe the course of immediate-type occupational asthma after a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.4.7921450
更新日期:1994-10-01 00:00:00
abstract:RATIONALE:Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment. OBJECTIVES:To characterize the blood genomic response in pat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201502-0355OC
更新日期:2015-10-01 00:00:00
abstract::A noninvasive means of detecting airway secretions in ventilator-dependent patients is desirable because endotracheal suctioning can result in life-threatening complications. In a patient who had copious secretions, we observed a sawtooth pattern on his flow-volume curve that disappeared after suctioning. Accordingly,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.3.8087350
更新日期:1994-09-01 00:00:00
abstract::In mechanically ventilated neonates, the instrumental dead space is a major determinant of total minute ventilation. By flushing this dead space, continuous tracheal gas insufflation (CTGI) may allow reduction of the risk of overinflation. We conducted a randomized trial to evaluate the efficacy of CTGI in reducing ai...
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.162.3.9910063
更新日期:2000-09-01 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:From the late 1970s to the early 1990s, studies found that mortality rates for pulmonary fibrosis were increasing. Recent data for mortality from pulmonary fibrosis are unavailable. OBJECTIVES:We sought to determine mortality rates for pulmonary fibrosis in the United States from 1992 through 2003. METHODS:...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200701-044OC
更新日期:2007-08-01 00:00:00
abstract::Obstructive sleep apnea causes cardiovascular morbidity and premature death. Potential links between sleep apnea and cardiovascular complications are chronically elevated activity of the sympathetic nervous system and abnormal vascular function. To explore vascular function, we determined the reactive hyperemic blood ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.7.2102003
更新日期:2002-04-01 00:00:00
abstract:RATIONALE:Secondhand tobacco smoke (SHS) and traffic-related air pollutants are associated with asthma and allergy. Diesel exhaust particles (DEPs) and SHS can interact with allergens in exacerbating allergic airway diseases through generation of reactive oxygen species. Glutathione S-transferases (GSTs) metabolize rea...
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.200509-1424OC
更新日期:2006-12-15 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
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更新日期:2004-10-15 00:00:00
abstract::To determine the status of activation of lymphocytes and the role of cytokines on the inflammatory response of the bronchial mucosa in toluene diisocyanate (TDI) asthma, we performed a quantitative analysis of bronchial biopsies obtained from 15 subjects with TDI-induced asthma and seven normal control subjects. Marke...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.3.7533600
更新日期:1995-03-01 00:00:00
abstract::Prior data indicate positive effects of long-term exercise interventions for cognitive functioning among patients with chronic obstructive pulmonary disease (COPD), but no prior studies have examined acute effects of individual bouts of exercise among patients with COPD. This study evaluated acute effects of exercise ...
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.164.9.2104137
更新日期:2001-11-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is associated with several pathophysiological deficits found in diabetic retinopathy (DR). Hence, it's plausible that OSA could play a role in the pathogenesis of sight-threatening DR (STDR). OBJECTIVES:To assess the relationship between OSA and DR in patients with type 2 diabet...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201701-0175OC
更新日期:2017-10-01 00:00:00
abstract:RATIONALE:Exposure to combustion-derived air pollution is associated with an early (1-2 h) and sustained (24 h) rise in cardiovascular morbidity and mortality. We have previously demonstrated that inhalation of diesel exhaust causes an immediate (within 2 h) impairment of vascular and endothelial function in humans. O...
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.200606-872OC
更新日期:2007-08-15 00:00:00