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 positron emission tomography (PET) imaging of methacholine-induced bronchoconstriction in sheep. Regional VA/Q ratios were calculated from the imaged kinetics of intravenously injected 13NN-saline bolus, assembled into global VA/Q distributions, and used to estimate gas exchange. During bronchoconstriction, large regions with impaired tracer washout were observed adjacent to regions of normal ventilation. PET-derived VA/Q distributions during bronchoconstriction were consistently bimodal, with areas of low VA/Q receiving a large fraction of Q. The standard deviation of the VA/Q distribution was 38% lower if small-scale (subresolution) heterogeneity (< 2.2 cm3) was ignored. Arterial blood gases predicted from PET data correlated well with measured values for Pa(O2) (r2= 0.91, p < 0.01) and Pa(CO2) (r2= 0.90, p < 0.01). We conclude that the bimodality of VA/Q distributions in bronchoconstriction reflects the involvement of large contiguous regions of hypoventilation with substantial subresolution intraregional VA/Q heterogeneity. Assessment of the subresolution VA/Q heterogeneity is therefore essential to accurately quantify global gas exchange impairment during bronchoconstriction.
journal_name
Am J Respir Crit Care Medauthors
Melo MF,Harris RS,Layfield JD,Venegas JGdoi
10.1164/rccm.200409-1296OCkeywords:
subject
Has Abstractpub_date
2005-04-01 00:00:00pages
714-21issue
7eissn
1073-449Xissn
1535-4970pii
200409-1296OCjournal_volume
171pub_type
杂志文章abstract:RATIONALE:Recent studies have suggested that both embryonic stem cells and adult bone marrow stem cells can participate in the regeneration and repair of diseased adult organs, including the lungs. However, the extent of airway epithelial remodeling with adult marrow stem cells is low, and there are no available in viv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200706-859OC
更新日期:2008-04-01 00:00:00
abstract::To quantify changes in tissue oxygenation of pathologic lungs, we applied a novel method using near-infrared spectroscopy (NIRs). In in vitro experiments, we assayed the effect of photon scattering on the absorption spectra of an in vitro system simulating structures of lung, which consists of test tube containing air...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.5.97-01112
更新日期:1997-11-01 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: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 ...
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.200909-1448OC
更新日期:2010-04-15 00:00:00
abstract:RATIONALE:Regional hypoventilation in bronchoconstricted patients with asthma is spatially associated with reduced perfusion, which is proposed to result from hypoxic pulmonary vasoconstriction (HPV). OBJECTIVES:To determine the role of HPV in the regional perfusion redistribution in bronchoconstricted patients with a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201612-2438OC
更新日期:2017-10-01 00:00:00
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::The inflection points of the pressure-volume curve have been used for setting mechanical ventilation in patients with acute lung injury. However, the lung status at these points has never been specifically addressed. In 12 patients with early lung injury we traced both limbs of the pressure-volume curve by means of a ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200312-1644OC
更新日期:2004-11-15 00:00:00
abstract:RATIONALE:In the normal lung, breathing and deep inspirations potently antagonize bronchoconstriction, but in the asthmatic lung this salutary effect is substantially attenuated or even reversed. To explain these findings, the prevailing hypothesis focuses on contracting airway smooth muscle and posits a nonlinear dyna...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201202-0368OC
更新日期:2012-08-01 00:00:00
abstract::A study was done to compare the efficacy and safety of the coprescription of salmeterol 50 microgram twice daily or 100 microgram twice daily with beclomethasone dipropionate (BDP) 500 micrograms twice daily (SALM 50 and SALM 100) with BDP 1,000 microgram twice daily (BDP 1,000) in patients with asthma not controlled ...
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/ajrccm.153.5.8630590
更新日期:1996-05-01 00:00:00
abstract:RATIONALE:Patients with chronic obstructive pulmonary disease (COPD) show a poor response to corticosteroids. This has been linked to a reduction of histone deacetylase-2 as a result of oxidative stress and is reversed by theophylline. OBJECTIVES:To determine the role of phosphoinositide-3-kinase-delta (PI3K-δ) on the...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200906-0937OC
更新日期:2010-10-01 00:00:00
abstract::Bronchial overproduction of leukotrienes and inhibition of prostaglandin synthesis are involved in the pathogenesis of aspirin-induced asthma. We investigated whether inhaled prostaglandin E2 (PGE2) attenuates the response to bronchial challenge with lysine acetylsalicylate (LASA) and the associated increase in urinar...
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.153.2.8564100
更新日期:1996-02-01 00:00:00
abstract:RATIONALE:Respiratory syncytial virus (RSV) is the leading cause of childhood lower respiratory infection, yet viable therapies are lacking. Two major challenges have stalled antiviral development: ethical difficulties in performing pediatric proof-of-concept studies and the prevailing concept that the disease is immun...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201002-0221OC
更新日期:2010-11-15 00:00:00
abstract::An imbalance between neutrophil proteases and the surrounding antiproteases is critical in the normal functioning of the neutrophil. Enzyme activity is of importance in cell migration and may play a role in some beneficial aspects of host defense. However, when persistent or excessive this imbalance can be detrimental...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.160.supplement_1.13
更新日期:1999-11-01 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::A higher exposure to endotoxin was hypothesized to contribute to lower prevalence of allergic sensitization and hay fever in children growing up on a farm. We studied the association between house dust endotoxin and allergic sensitization. We randomly selected 740 children, aged between 5 and 10 years, from a group of...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-256OC
更新日期:2002-10-01 00:00:00
abstract::To assess whether there is increased risk of tuberculous infection in children who traveled to or had a household visitor from a country having a high prevalence of tuberculosis, we conducted a case-control study. Children younger than 6 yr of age who had a tuberculin skin test read at public health clinics in areas o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.6.9804106
更新日期:1998-12-01 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:RATIONALE:Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. OBJECTIVE:We evaluated whether t...
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/rccm.200503-458OC
更新日期:2005-10-01 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
doi:10.1164/rccm.200305-682OC
更新日期:2003-12-01 00:00:00
abstract::The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.5.7952560
更新日期:1994-11-01 00:00:00
abstract::Changes in dynamic lung compliance during inspiration and expiration cannot be modeled accurately with conventional algorithms. We developed a simple method to analyze pressure-volume (P/V) relationships under condition of nonlinearity (APVNL) and tested it in a lung model with known resistance and nonlinear P/V relat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.4.9801011
更新日期:1998-10-01 00:00:00
abstract::Sepsis is the most common cause of death in patients in the intensive care unit. Genome-wide gene expression analysis can provide insights into the molecular alterations of sepsis. Total mRNA was extracted from the livers of 6 uninfected control mice and 60 septic mice after infusion of either live Escherichia coli or...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200211-1278OC
更新日期:2004-05-15 00:00:00
abstract:RATIONALE:Diesel motor exhaust is classified by the International Agency for Research on Cancer as probably carcinogenic to humans. The epidemiologic evidence is evaluated as limited because most studies lack adequate control for potential confounders and only a few studies have reported on exposure-response relationsh...
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.201006-0940OC
更新日期:2011-04-01 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::Selected events in rhinovirus infection of the normal human airway can be regarded as occurring sequentially. Initial steps in rhinovirus pathogenesis are believed to include viral entry into the nose, mucociliary transport of virus to the posterior pharynx, and initiation of infection in ciliated and non-ciliated epi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm/152.4_Pt_2.S36
更新日期:1995-10-01 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:RATIONALE:In the absence of a surgical lung biopsy, patients diagnosed with idiopathic pulmonary fibrosis (IPF) in clinical practice could participate in the INPULSIS trials of nintedanib if they had honeycombing and/or traction bronchiectasis plus reticulation, without atypical features of usual interstitial pneumonia...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201602-0402OC
更新日期:2017-01-01 00:00:00
abstract:RATIONALE:There is conflicting information about the development and resolution of airway inflammation and airway hyperresponsiveness (AHR) after repeated airway exposure to allergen in sensitized mice. METHODS:Sensitized BALB/c and C57BL/6 mice were exposed to repeated allergen challenge on 3, 7, or 11 occasions. Air...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200505-783OC
更新日期:2006-01-01 00:00:00
abstract:RATIONALE:In 1989, the United States embarked upon an ambitious path to eliminate tuberculosis (TB) nationwide. Although incidence rates of TB disease in the United States are declining, these cases represent only a tiny fraction of all TB infections. Understanding national trends in TB infection may be important in an...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200706-950OC
更新日期:2008-02-15 00:00:00
abstract::Many patients who develop incapacitating illness have not expressed clear treatment preferences. Therefore, surrogate decision makers are asked to make judgments about what treatment pathway is most consistent with the patient's values. Surrogates often struggle with such decisions. The difficulty arises because answe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/rccm.201204-0710CP
更新日期:2012-09-15 00:00:00