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Safety of incremental inhaled lipopolysaccharide challenge in humans

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA, sundy001{at}mc.duke.edu

William A. Wood

Harvard Combined Medicine/Pediatrics Training Program, Massachusetts General Hospital, Boston, Massachusetts, USA

Janet L. Watt

Department of Medicine, University of Iowa, Iowa City, Iowa, USA

Joel N. Kline

Department of Medicine, University of Iowa, Iowa City, Iowa, USA

David A. Schwartz

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA

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 µg 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.

Key Words: Lipopolysaccharide • endotoxin • inhalation challenge • systemic responses

Journal of Endotoxin Research, Vol. 12, No. 2, 113-119 (2006)
DOI: 10.1177/09680519060120020701


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