AsthmaNCT00005550
Endotoxin and Bronchial Inflammation in Asthma
An observational study of Asthma and Lung Diseases, run by University of North Carolina, Chapel Hill.
Trial summary
To evaluate airway inflammation in persons with asthma exposed to endotoxin, a common occupational air contaminant. Subjects are subsequently challenged with allergen. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Asthma, Lung Diseases, Inflammation
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- Jan 1999to Dec 2006
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To evaluate airway inflammation in persons with asthma exposed to endotoxin, a common occupational air contaminant. Subjects are subsequently challenged with allergen.
Read the 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.
- Conditions
- Asthma, Lung Diseases, Inflammation
- Medical subject headings
- Asthma, Lung Diseases, Inflammation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startJan 1999
- Primary completionDec 2006
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, David B. Peden, MD, University of North Carolina, Chapel Hill
- Investigators
- David Peden, University of North Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005550
- Sponsor's protocol ID
- 5094
- Other IDs
- R01HL062624
- Status last verified
- Aug 2014
- First submitted
- 25 May 2000
- Last updated
- 11 Aug 2014
- Results posted
- No
Publications
Alexis N, Eldridge M, Reed W, Bromberg P, Peden DB. CD14-dependent airway neutrophil response to inhaled LPS: role of atopy. J Allergy Clin Immunol. 2001 Jan;107(1):31-5. doi: 10.1067/mai.2001.111594.
PubMed 11149987Eldridge MW, Peden DB. Airway response to concomitant exposure with endotoxin and allergen in atopic asthmatics. J Toxicol Environ Health A. 2000 Sep 15;61(1):27-37. doi: 10.1080/00984100050116762.
PubMed 10990161Eldridge MW, Peden DB. Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma. J Allergy Clin Immunol. 2000 Mar;105(3):475-81. doi: 10.1067/mai.2000.104552.
PubMed 10719296Alexis NE, Peden DB. Blunting airway eosinophilic inflammation results in a decreased airway neutrophil response to inhaled LPS in patients with atopic asthma: a role for CD14. J Allergy Clin Immunol. 2001 Oct;108(4):577-80. doi: 10.1067/mai.2001.118511.
PubMed 11590384Alexis NE, Eldridge MW, Peden DB. Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects. J Allergy Clin Immunol. 2003 Aug;112(2):353-61. doi: 10.1067/mai.2003.1651.
PubMed 12897742Alexis NE, Becker S, Bromberg PA, Devlin R, Peden DB. Circulating CD11b expression correlates with the neutrophil response and airway mCD14 expression is enhanced following ozone exposure in humans. Clin Immunol. 2004 Apr;111(1):126-31. doi: 10.1016/j.clim.2003.12.002.
PubMed 15093561Alexis NE, Lay JC, Almond M, Peden DB. Inhalation of low-dose endotoxin favors local T(H)2 response and primes airway phagocytes in vivo. J Allergy Clin Immunol. 2004 Dec;114(6):1325-31. doi: 10.1016/j.jaci.2004.09.002.
PubMed 15577830
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endotoxin and Bronchial Inflammation in Asthma
- ClinicalTrials.gov ID
- NCT00005550
- Acronym / sponsor ID
- 5094
- Conditions
- Asthma, Lung Diseases, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 1999
- Primary completion
- Dec 2006 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 26 May 2000 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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.
Study design
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2014.
- Background: PubMed 11149987Alexis N, Eldridge M, Reed W, Bromberg P, Peden DB. CD14-dependent airway neutrophil response to inhaled LPS: role of atopy. J Allergy Clin Immunol. 2001 Jan;107(1):31-5. doi: 10.1067/mai.2001.111594.
- Background: PubMed 10990161Eldridge MW, Peden DB. Airway response to concomitant exposure with endotoxin and allergen in atopic asthmatics. J Toxicol Environ Health A. 2000 Sep 15;61(1):27-37. doi: 10.1080/00984100050116762.
- Background: PubMed 10719296Eldridge MW, Peden DB. Allergen provocation augments endotoxin-induced nasal inflammation in subjects with atopic asthma. J Allergy Clin Immunol. 2000 Mar;105(3):475-81. doi: 10.1067/mai.2000.104552.
- Background: PubMed 11590384Alexis NE, Peden DB. Blunting airway eosinophilic inflammation results in a decreased airway neutrophil response to inhaled LPS in patients with atopic asthma: a role for CD14. J Allergy Clin Immunol. 2001 Oct;108(4):577-80. doi: 10.1067/mai.2001.118511.
- Background: PubMed 12897742Alexis NE, Eldridge MW, Peden DB. Effect of inhaled endotoxin on airway and circulating inflammatory cell phagocytosis and CD11b expression in atopic asthmatic subjects. J Allergy Clin Immunol. 2003 Aug;112(2):353-61. doi: 10.1067/mai.2003.1651.
- Background: PubMed 15093561Alexis NE, Becker S, Bromberg PA, Devlin R, Peden DB. Circulating CD11b expression correlates with the neutrophil response and airway mCD14 expression is enhanced following ozone exposure in humans. Clin Immunol. 2004 Apr;111(1):126-31. doi: 10.1016/j.clim.2003.12.002.
- Background: PubMed 15577830Alexis NE, Lay JC, Almond M, Peden DB. Inhalation of low-dose endotoxin favors local T(H)2 response and primes airway phagocytes in vivo. J Allergy Clin Immunol. 2004 Dec;114(6):1325-31. doi: 10.1016/j.jaci.2004.09.002.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David Peden
University of North Carolina
Questions about this trial
What is this clinical trial studying?
An observational study of Asthma and Lung Diseases, run by University of North Carolina, Chapel Hill.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005550, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2014.