Abstract:
:Noninflammatory structural alterations, variously referred to as airway remodeling, are well documented in the asthmatic airway. However, the pathogenesis of these alterations, the importance of airway remodeling in generating the asthma phenotype, and the natural history of airway remodeling responses have not been adequately defined. Because exaggerated cytokine production is a characteristic feature of the asthmatic airway, we used constitutive and inducible overexpression transgenic systems to investigate the contributions that interleukin 11 (IL-11) and IL-13 might make to airway remodeling responses. These studies demonstrated that both cytokines produce responses in the murine airway with features similar to those in human asthmatic tissues. IL-11 caused airway fibrosis with the enhanced accumulation of interstitial collagens, myocytes, and myofibroblasts. IL-13 caused mucous metaplasia, enhanced mucin gene expression, enhanced tissue hyaluronic acid accumulation, and subepithelial fibrosis. Importantly, IL-11 was detected most readily in tissues from asthmatic subjects with severe airway remodeling that was similar to that seen in the IL-11 transgenic mice. In addition, IL-11 was shown to inhibit asthma-like inflammation while stimulating airway fibrosis. This suggests that IL-11 elaboration is, in part, an attempt at airway healing. Last, a novel triple transgenic system is described that allows transgene expression to be regulated in a true "on/off" manner. This system may be useful in defining the reversibility of transgene-induced airway remodeling responses.
journal_name
Am J Respir Crit Care Medauthors
Zhu Z,Lee CG,Zheng T,Chupp G,Wang J,Homer RJ,Noble PW,Hamid Q,Elias JAdoi
10.1164/ajrccm.164.supplement_2.2106070keywords:
subject
Has Abstractpub_date
2001-11-15 00:00:00pages
S67-70issue
10 Pt 2eissn
1073-449Xissn
1535-4970journal_volume
164pub_type
杂志文章abstract::The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200402-215OC
更新日期:2004-12-01 00:00:00
abstract:RATIONALE:Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. OBJECTIVES:To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respirator...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-782OC
更新日期:2006-12-15 00:00:00
abstract::Bronchial dehiscence after lung transplantation is difficult to treat and associated with high mortality. We describe our experience using self-expanding metallic stents to treat post-lung transplant bronchial dehiscence. From January 1995 to June 2004, 189 single and 118 double lung transplants were performed in our ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200410-1388OC
更新日期:2005-09-15 00:00:00
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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::Epidemiologic investigation has established an association between exposure to particulate matter (PM) and human health in the Utah Valley. Reduction of particle mass during the temporary closure of a local steel mill was associated with diminished morbidity and mortality. We tested the hypothesis that the biologic ef...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2011089
更新日期:2001-08-15 00:00:00
abstract::Patients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activi...
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:2003-12-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201003-0477OC
更新日期:2010-10-01 00:00:00
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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
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doi:10.1164/rccm.201105-0834OC
更新日期:2012-01-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201404-0720OC
更新日期:2014-11-01 00:00:00
abstract::Ethane is a product of lipid peroxidation as a result of oxidative stress and can be detected in the exhaled air. Oxidative stress plays a role in the pathogenesis of asthma. We measured exhaled ethane in 26 asthmatic subjects (mean age +/- SEM, 38 +/- 8 yr; 15 male, FEV(1) 60 +/- 4%) and compared it with exhaled nitr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.4.2003064
更新日期:2000-10-01 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:RATIONALE:chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by speci...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201004-0541OC
更新日期:2011-01-01 00:00:00
abstract:RATIONALE:Cystic fibrosis (CF) lung disease is caused by the loss of function of the cystic fibrosis transmembrane conductance regulator (CFTR) combined with hyperactivation of the epithelial sodium channel (ENaC). In the lung, ENaC is responsible for movement of sodium. Hyperactivation of ENaC, which creates an osmoti...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201612-2445OC
更新日期:2017-09-15 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201004-0654OC
更新日期:2011-04-01 00:00:00
abstract::This study was designed to evaluate the value and applicability of tidal breathing pattern analysis to assess airflow obstruction in young children. The time needed to reach maximal tidal expiratory flow (TME) divided by total expiratory time (TE) was measured in 228 healthy children 3 to 11 yr of age, 64 patients wit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.4.8616550
更新日期:1996-04-01 00:00:00
abstract::We hypothesized that a leukotriene receptor antagonist (LTRA) could provide bronchoprotection against the cold, dry air-induced response in asthmatic preschool children. In a randomized, double-blind, placebo-controlled crossover study, we examined the effect of the specific LTRA montelukast at 5 mg/d for 2 d on the b...
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.162.1.9910039
更新日期:2000-07-01 00:00:00
abstract::Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of the epithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (approximately 120-140/cell) on the cell surface. The microvilli cont...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
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更新日期:2005-07-01 00:00:00
abstract::The distribution of ventilation-perfusion (VA/Q) ratios during bronchoconstriction measured with the multiple inert gases elimination technique is frequently bimodal. However, the topographic basis and the cause of that bimodality remain unknown. In this article, regional VA/Q is quantified by three-dimensional positr...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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更新日期:2005-04-01 00:00:00
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.4.8887600
更新日期:1996-10-01 00:00:00
abstract::Although there is abundant clinical evidence of asthmatic responses to indoor aeroallergens, the symptomatic impacts of other common indoor air pollutants from gas stoves, fireplaces, and environmental tobacco smoke have been less well characterized. These combustion sources produce a complex mixture of pollutants, ma...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.149.6.8004290
更新日期:1994-06-01 00:00:00
abstract::The role of strain difference in the response to cigarette smoke was investigated in mice. Mice of the strains DBA/2 and C57BL/6J responded to acute cigarette smoke with a decrease of the antioxidant defenses of their bronchoalveolar lavage (BAL) fluids. On the other hand, under these conditions ICR mice increased the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.5.2010032
更新日期:2001-09-01 00:00:00
abstract::To investigate the effect of smoking cessation on the airway inflammatory process present in nonatopic subjects with chronic bronchitis, we obtained bronchial biopsies from nine current smokers and seven exsmokers, all with symptoms of chronic bronchitis at the time of the study, and from seven healthy nonsmoking subj...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.4.7551380
更新日期:1995-10-01 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
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journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201311-1971OC
更新日期:2014-09-01 00:00:00
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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::An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disod...
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.156.5.9611088
更新日期:1997-11-01 00:00:00
abstract::Superoxide dismutase (SOD) is a ubiquitous metalloenzyme in aerobic organisms that catalyzes the conversion of superoxide anion to hydrogen peroxide. Mycobacterium tuberculosis is unusual in that it secretes large quantities of iron-cofactored SOD. To determine the role of SOD in pathogenesis, we constructed mutants o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.12.2106093
更新日期:2001-12-15 00:00:00
abstract::In asthma, the acute increment of airway responsiveness caused by exposure to allergen is associated with influx of eosinophils into the airways. The relationship between chronic airway hyperresponsiveness and airway inflammation is unclear, as they do not change consistently following long-term anti-inflammatory trea...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.1.9703002
更新日期:1998-01-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA), a treatable sleep disorder that is associated with alterations in glucose metabolism in individuals without diabetes, is a highly prevalent comorbidity of type 2 diabetes. However, it is not known whether the severity of OSA is a predictor of glycemic control in patients with di...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1423OC
更新日期:2010-03-01 00:00:00