Endotoxin and Bronchial Inflammation in Asthma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
David B. Peden, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT00005550
First received: May 25, 2000
Last updated: August 8, 2014
Last verified: August 2014
  Purpose

To evaluate airway inflammation in persons with asthma exposed to endotoxin, a common occupational air contaminant. Subjects are subsequently challenged with allergen.


Condition
Asthma
Lung Diseases
Inflammation

Study Type: Observational

Resource links provided by NLM:


Further study details as provided by University of North Carolina, Chapel Hill:

Study Start Date: January 1999
Study Completion Date: December 2006
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Endotoxin (or lipopolysaccharide [LPS]) is a potent inflammatory stimulant which is found in ambient air in occupational settings. Asthma in the workplace is an increasingly significant problem. Asthma is characterized by airway inflammation and increased reactivity to both allergic and non-allergic stimuli. LPS is known to induced airway inflammation in normal subjects and to enhance airway reactivity in asthmatics. Additionally, both alveolar macrophages and mononuclear cells from asthmatics secrete higher amounts of cytokines (interleukins 1 and 8 [IL-1, IL-8] and granulocyte macrophage-colony stimulating factor [GM-CSF] ) than those from normals. Thus, it is likely that LPS enhances allergen-induced inflammation and that allergic asthmatics are more sensitive to the effects of LPS. Preliminary data show that exposure to low levels (250 ng/m3) of LPS at risk for four hours enhances both immediate responsiveness to inhaled allergen and allergen-induced eosinophils as observed in induced sputum. In the nasal airways of allergics, a single dose of 1,000 nanograms of LPS enhances polymorphonuclear leukocyte influx associated with allergen challenge. This latter finding also correlates well with baseline IL-8 and ECP levels, suggesting that constitutive airway inflammation enhances response to these stimuli.

DESIGN NARRATIVE:

The effect of endotoxin LPS (5,000 nanograms) is compared on airway inflammation and methacholine response and lung function in normals and asthmatics; the effect of LPS (500 nanograms) is compared on allergen-induced reactivity and inflammatory cell influx following LPS exposure (5,000 nanograms) in asthmatics, likely as a result of decreasing baseline inflammation. To examine potential cellular mediation of the effect of LPS in asthma, cytokine secretion of mononuclear cells to LPS of subjects responding to LPS (or those in whom LPS enhance response to allergen) is compared to those who did not respond. In vitro monocyte and in vivo airway responses of asthmatics who are responsive and non-responsive is compared to baseline sputum and nasal lavage fluid IL-8 and ECP to determine if either in vitro monocyte responses or IL-8 and ECP in readily obtained airway fluids may serve as biomarkers of LPS responsiveness and might be used as a marker for a LPS-response phenotype in humans for future mechanistic and intervention studies. Finally, practical data on the effect of LPS in asthmatics (at levels found in typical work settings) and the ability of standard anti-inflammatory therapy to protect asthmatic workers unavoidable exposed to LPS will be obtained.

The study was renewed in 2001 and continues through December, 2005.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00005550

Sponsors and Collaborators
University of North Carolina, Chapel Hill
Investigators
Investigator: David Peden University of North Carolina
  More Information

Publications:
Responsible Party: David B. Peden, MD, Professor of Pediatrics, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT00005550     History of Changes
Other Study ID Numbers: 5094, R01HL062624
Study First Received: May 25, 2000
Last Updated: August 8, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Asthma
Inflammation
Lung Diseases
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on August 18, 2014