Ignite Creation Date:
2024-05-05 @ 10:22 AM
Last Modification Date:
2024-10-26 @ 9:05 AM
Study NCT ID:
NCT00005550
Status:
COMPLETED
Last Update Posted:
2014-08-11
First Post:
2000-05-25
Brief Title:
Endotoxin and Bronchial Inflammation in Asthma
Sponsor:
University of North Carolina Chapel Hill
Organization:
University of North Carolina Chapel Hill
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2014-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
To evaluate airway inflammation in persons with asthma exposed to endotoxin a common occupational air contaminant Subjects are subsequently challenged with allergen
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 ngm3 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 1000 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 5000 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 5000 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
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 ngm3 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 1000 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 5000 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 5000 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
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| R01HL062624 | NIH | None | httpsreporternihgovquickSearchR01HL062624 |