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 immune-mediated rather than being driven by viral load. OBJECTIVES:The development of a human experimental wild-type RSV infection model to address these challenges. METHODS:Healthy volunteers (n = 35), in five cohorts, received increasing quantities (3.0-5.4 log plaque-forming units/person) of wild-type RSV-A intranasally. MEASUREMENTS AND MAIN RESULTS:Overall, 77% of volunteers consistently shed virus. Infection rate, viral loads, disease severity, and safety were similar between cohorts and were unrelated to quantity of RSV received. Symptoms began near the time of initial viral detection, peaked in severity near when viral load peaked, and subsided as viral loads (measured by real-time polymerase chain reaction) slowly declined. Viral loads correlated significantly with intranasal proinflammatory cytokine concentrations (IL-6 and IL-8). Increased viral load correlated consistently with increases in multiple different disease measurements (symptoms, physical examination, and amount of nasal mucus). CONCLUSIONS:Viral load appears to drive disease manifestations in humans with RSV infection. The observed parallel viral and disease kinetics support a potential clinical benefit of RSV antivirals. This reproducible model facilitates the development of future RSV therapeutics.
journal_name
Am J Respir Crit Care Medauthors
DeVincenzo JP,Wilkinson T,Vaishnaw A,Cehelsky J,Meyers R,Nochur S,Harrison L,Meeking P,Mann A,Moane E,Oxford J,Pareek R,Moore R,Walsh E,Studholme R,Dorsett P,Alvarez R,Lambkin-Williams Rdoi
10.1164/rccm.201002-0221OCsubject
Has Abstractpub_date
2010-11-15 00:00:00pages
1305-14issue
10eissn
1073-449Xissn
1535-4970pii
201002-0221OCjournal_volume
182pub_type
临床试验,杂志文章abstract::We determined if pulmonary peptidoleukotrienes contribute to the pathogenesis of chronic lung disease of extreme prematurity (CLD) by measuring urinary leukotriene E4 (uLTE4). Study patients had a birth weight < 1000 g and were about 28 d old when they were classified as normal control subjects (n = 8) or as having CL...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.3_Pt_1.841
更新日期:1995-03-01 00:00:00
abstract::Colony-forming units of Mycobacterium tuberculosis in sputum were counted at 2-day intervals in 100 patients treated with 22 regimens of isoniazid, rifampin, pyrazinamide, ethambutol, or streptomycin, given alone or in combinations. The exponential fall in colony-forming units was measured by linear regression coeffic...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200210-1125OC
更新日期:2003-05-15 00:00:00
abstract:RATIONALE:The sympathetic nervous system has been reported to be activated in pulmonary arterial hypertension (PAH). OBJECTIVES:We investigated the prognostic significance of muscle sympathetic nervous system activity (MSNA) in PAH. METHODS:Thirty-two patients with PAH were included in the study and underwent a measu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200912-1856OC
更新日期:2010-06-01 00:00:00
abstract::Impaired lung epithelial Na(+) channel (ENaC) activity at the time of birth results in respiratory distress. To investigate potential mechanisms, the ontogeny and cellular distribution of the alphaENaC subunit mRNA expression was studied in normal, immature, and abnormal (hypoplastic) human fetal lungs using nonradioi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.4.9905064
更新日期:2000-04-01 00:00:00
abstract::To define the mechanisms by which inhaled glucocorticosteroid regulates allergen-induced airway inflammation, a double-blind, placebo-controlled, cross-over study with inhaled budesonide was conducted in 14 subjects with allergic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were rando...
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.162.3.9910077
更新日期:2000-09-01 00:00:00
abstract:RATIONALE:Exacerbation of chronic obstructive pulmonary disease commonly causes hospitalization. The change in lung mechanics during exacerbation and its relationship to symptoms in spontaneously breathing individuals has not been described. OBJECTIVE:We hypothesized that changes in both airflow and lung volumes would...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200504-595OC
更新日期:2005-12-15 00:00:00
abstract::It has been nearly a century since the first suggestion that a soluble factor in plasma or serum might be responsible for the symptoms of allergic disease and asthma, and more than 30 yr since immunoglobulin E (IgE) was identified as the key molecule in mediating what are now described as type 1 hypersensitivity react...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.164.supplement_1.2103024
更新日期:2001-10-15 00:00:00
abstract:RATIONALE:Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear. OBJECTIVES:We hypothesized that formation of a fibrin mesh retains plasma protei...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201207-1292OC
更新日期:2013-01-01 00:00:00
abstract::Effects of nitric oxide (NO) and aerosolized terbutaline inhalation on ventilation-perfusion (VA/Q) distributions were determined during methacholine-induced bronchoconstriction in nine mechanically ventilated pigs. Animals inhaled, in random order, zero, 20, and 80 parts per million (ppm) of NO or aerosolized terbuta...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.151.1.7812540
更新日期:1995-01-01 00:00:00
abstract::Endothelins (ET-1, ET-2, ET-3) are potent bronchoconstrictors and growth-promoting mediators. They are released from various cells such as endothelial and epithelial cells. In the airways, ETs are released under basal and stimulated conditions. In patients with status asthmaticus and other pulmonary disorders, the exp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.6.9196090
更新日期:1997-06-01 00:00:00
abstract::This study was carried out to determine if the bronchoconstrictive effect of cigarette smoke (CS) is enhanced when airway hyperresponsiveness is induced by ovalbumin (Ova) sensitization, and if so, whether an increase in endogenously released tachykinins is involved. The bronchoconstrictive effects of an acute CS inha...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9809121
更新日期:2000-01-01 00:00:00
abstract::Secretory leukocyte protease inhibitor (SLPI) and elafin are structurally similar, low-molecular-weight antiproteases produced in the lung. We have developed a simple method for distinguishing the antiprotease activities of SLPI and elafin in lung lavage fluid from those of alpha 1-antitrypsin (alpha 1-AT) that is bas...
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.152.5.7582300
更新日期:1995-11-01 00:00:00
abstract::Although hematopoietic stem cell transplantation (HSCT) can be curative in patients with certain malignancies, survival is poor if the recipient becomes critically ill. This prospective study examined the outcomes of 115 consecutive HSCT patients admitted to the medical intensive care unit (MICU) of a tertiary cancer ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.3.9711076
更新日期:1998-09-01 00:00:00
abstract::Early experience suggests that lung volume reduction surgery improves exercise tolerance as measured by the 6-min walk distance in patients with emphysema. To identify the physiologic mechanism(s) by which lung volume reduction surgery improved exercise, we performed progressive cardiopulmonary exercise testing, inclu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.2.9611032
更新日期:1997-08-01 00:00:00
abstract:RATIONALE:Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. OBJECTIVES:Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) ge...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200412-1708OC
更新日期:2005-07-01 00:00:00
abstract::The aim of the study was to determine whether closing pressures or vascular distensibility can be used to describe liver venous hemodynamics when right atrial pressure is raised. The study was performed using a vascularly isolated pig liver preparation that allowed the independent control of portal vein and hepatic ar...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.2.7633700
更新日期:1995-08-01 00:00:00
abstract:RATIONALE:Neutrophils are usually the first circulating leukocytes to respond during bacterial pneumonia. Their expression of oxidants, proteases, and other mediators present in granules is well documented, but their ability to produce mediators through transcription and translation after migration to an inflammatory s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201004-0592OC
更新日期:2011-05-15 00:00:00
abstract:RATIONALE:Platelets are essential for pulmonary leukocyte recruitment, airway hyperresponsiveness, and bronchial remodeling in animals with allergic inflammation and can be found in bronchoalveolar lavage of sensitized animals. No studies, however, have explored the direct migration of platelets to lungs. OBJECTIVES:T...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200702-214OC
更新日期:2008-03-15 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrotic disorder underlain by aberrant wound healing of repeated lung injury. Environmental triggers and genetic background are likely to act as modifiers of the fibrotic response. Erythrocyte complement receptor 1 is a membrane protein mediating the transport of immu...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200302-221OC
更新日期:2003-08-01 00:00:00
abstract:RATIONALE:Severe pulmonary arterial hypertension (PAH) is characterized by the formation of plexiform lesions and concentric intimal fibrosis in small pulmonary arteries. The origin of cells contributing to these vascular lesions is uncertain. Endogenous endothelial progenitor cells are potential contributors to this p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200810-1662OC
更新日期:2009-10-15 00:00:00
abstract:RATIONALE:Amplification of distal 3q is the most common genomic aberration in squamous lung cancer (SQC). SQC develops in a multistage progression from normal bronchial epithelium through dysplasia to invasive disease. Identifying the key driver events in the early pathogenesis of SQC will facilitate the search for pre...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201001-0005OC
更新日期:2010-07-01 00:00:00
abstract::To investigate patterns of testing for human immunodeficiency virus (HIV) infection in tuberculosis patients, we obtained data from the tuberculosis registry and from medical records of 500 tuberculosis patients in Los Angeles County. Sixty-three percent of tuberculosis patients were tested for HIV infection, and mult...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.1.9001340
更新日期:1997-01-01 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
doi:10.1164/rccm.200409-1296OC
更新日期:2005-04-01 00:00:00
abstract::Infection of the cystic fibrosis (CF) airways elicits an exaggerated, interleukin-8 (IL-8) mediated, neutrophil inflammatory response. Necrosing neutrophils release DNA and actin into the airways, increasing the viscoelasticity of airway secretions. Mucolytics aim to improve airway clearance by reducing this viscoelas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.5.9908107
更新日期:2000-11-01 00:00:00
abstract:RATIONALE:Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear. OBJECTIVES:We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a res...
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
abstract:RATIONALE:Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency, a more rapid decline in lung function, and increased mortality in patients with bronchiectasis. OBJECTIVES:To perform a randomized placebo-controlled study assessing the efficacy and safety of inhaled colist...
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.201312-2208OC
更新日期:2014-04-15 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:RATIONALE:The rate of progression of most interstitial lung diseases (ILD) is unpredictable. Fibrocytes are circulating bone marrow-derived cells that have been implicated in the pathogenesis of lung fibrosis. Hermansky-Pudlak syndrome (HPS), a genetic cause of ILD in early adulthood, allows for study of biomarkers of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201407-1287OC
更新日期:2014-12-15 00:00:00
abstract::We described here an original device for laser Doppler (LD) flowmetry measurements of gastric mucosal perfusion, which was used here in healthy volunteers. A modified nasogastric tube containing the LD probe was inserted. Aspiration via a catheter, fixed in parallel to the probe, held the probe against the gastric wal...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.6.8970350
更新日期:1996-12-01 00:00:00
abstract::Four hundred forty-one subjects 34 to 69 yr of age were recruited from a random sample of the community. The sample was biased in favor of men, snorers, and subjects with subjective sleep complaints. They answered a questionnaire and were monitored in their homes for sleep-disordered breathing (SDB). This report conce...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.2.7633730
更新日期:1995-08-01 00:00:00