Document Detail


Safety of incremental inhaled lipopolysaccharide challenge in humans.
MedLine Citation:
PMID:  16690014     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Inhalation of environmental endotoxin is important in the pathogenesis of asthma and other environmental airway diseases. Inhaled airway challenge using lipopolysaccharide in humans has been performed for over 20 years to assess the airway response to endotoxin. However, there are no published data on the short-term safety of endotoxin inhalation protocols. OBJECTIVE: To characterize the safety and tolerability of incremental inhaled lipopolysaccharide challenge in humans. PATIENTS AND METHODS: We performed a retrospective analysis of data obtained from 119 subjects who underwent inhaled challenge with up to 41.5 mug of lipopolysaccharide. We measured pulmonary function, temperature, mean arterial pressure, heart rate, and systemic symptoms for 3 h after challenge. RESULTS: Fever occurred in 30% of subjects and was associated with a higher cumulative dose of lipopolysaccharide. Reduced mean arterial pressure occurred in 21% of subjects and was dose-related. There was no association between fever or decreased mean arterial pressure and airway responsiveness to inhaled lipopolysaccharide. Common symptoms reported by subjects included: chills (64%), malaise (56%), cough (56%), chest tightness (49%), headache (43%), and myalgias (27%). None of the subjects experienced delayed discharge or a serious adverse event. CONCLUSIONS: Inhaled lipopolysaccharide causes dose-related systemic responses that include fever, reduced blood pressure, and constitutional symptoms that are not associated with the airway response to inhaled lipopolysaccharide. Systemic responses to inhaled lipopolysaccharide should be expected and subjects undergoing inhaled lipopolysaccharide challenge in the research setting should be carefully monitored for non-pulmonary adverse events for several hours after challenge.
Authors:
John S Sundy; William A Wood; Janet L Watt; Joel N Kline; David A Schwartz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Journal of endotoxin research     Volume:  12     ISSN:  0968-0519     ISO Abbreviation:  J. Endotoxin Res.     Publication Date:  2006  
Date Detail:
Created Date:  2006-05-12     Completed Date:  2006-05-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9433350     Medline TA:  J Endotoxin Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  113-9     Citation Subset:  IM    
Affiliation:
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. sundy001@mc.duke.edu
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MeSH Terms
Descriptor/Qualifier:
Administration, Inhalation
Adolescent
Adult
Blood Pressure / drug effects
Body Temperature / drug effects
Dose-Response Relationship, Drug
Escherichia coli / chemistry
Female
Fever / chemically induced,  physiopathology
Heart Rate / drug effects
Humans
Lipopolysaccharides / administration & dosage,  toxicity*
Male
Middle Aged
Respiratory Function Tests
Retrospective Studies
Grant Support
ID/Acronym/Agency:
ES 11185/ES/NIEHS NIH HHS; ES 11375/ES/NIEHS NIH HHS; ES 12496/ES/NIEHS NIH HHS; ES005605/ES/NIEHS NIH HHS; ES07498/ES/NIEHS NIH HHS; RR00059/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Lipopolysaccharides

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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