Fluticasone Propionate Protects against Ozone-Induced Airway Inflammation and Modified Immune Cell Activation Markers in Healthy Volunteers.
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| Title: | Fluticasone Propionate Protects against Ozone-Induced Airway Inflammation and Modified Immune Cell Activation Markers in Healthy Volunteers. |
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| Authors: | Alexis, Neil E.1,2 Neil_Alexis@med.unc.edu, Lay, John C.1, Haczku, Angela3, Gong, Henry4,5, Linn, William4,5, Hazucha, Milan J.1, Harris, Brad1, Tal-Singer, Ruth6, Peden, David B.1,2 |
| Source: | Environmental Health Perspectives. Jun2008, Vol. 116 Issue 6, p799-805. 7p. 1 Diagram, 2 Charts, 3 Graphs. |
| Subject Terms: | *Physiological effects of ozone, *Biomarkers, Adrenocortical hormones, Asthma treatment, Inhalers, Immunology of inflammation, Sputum examination, Neutrophils |
| Abstract: | BACKGROUND: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O3-induced airway inflammation, but their effect on innate immune activation is unknown. OBJECTIVES: We used a human O3 inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers. METHODS: Seventeen O3-responsive subjects [> 10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O3 challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O3 challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation. RESULTS: FP had no effect on O3-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O3-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O3-induced modification of CD11b, mCD14, CD64, CD 16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner. CONCLUSION: This study confirmed and extended data demonstrating the protective effect of FP against O3-induced airway inflammation and immune cell activation. [ABSTRACT FROM AUTHOR] |
| Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | GreenFILE |
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| Header | DbId: 8gh DbLabel: GreenFILE An: 33142818 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Fluticasone Propionate Protects against Ozone-Induced Airway Inflammation and Modified Immune Cell Activation Markers in Healthy Volunteers. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Alexis%2C+Neil+E%2E%22">Alexis, Neil E.</searchLink><relatesTo>1,2</relatesTo><i> Neil_Alexis@med.unc.edu</i><br /><searchLink fieldCode="AR" term="%22Lay%2C+John+C%2E%22">Lay, John C.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Haczku%2C+Angela%22">Haczku, Angela</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Gong%2C+Henry%22">Gong, Henry</searchLink><relatesTo>4,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Linn%2C+William%22">Linn, William</searchLink><relatesTo>4,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Hazucha%2C+Milan+J%2E%22">Hazucha, Milan J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Harris%2C+Brad%22">Harris, Brad</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Tal-Singer%2C+Ruth%22">Tal-Singer, Ruth</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Peden%2C+David+B%2E%22">Peden, David B.</searchLink><relatesTo>1,2</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Jun2008, Vol. 116 Issue 6, p799-805. 7p. 1 Diagram, 2 Charts, 3 Graphs. – Name: Subject Label: Subject Terms Group: Su Data: *<searchLink fieldCode="DE" term="%22Physiological+effects+of+ozone%22">Physiological effects of ozone</searchLink><br />*<searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Adrenocortical+hormones%22">Adrenocortical hormones</searchLink><br /><searchLink fieldCode="DE" term="%22Asthma+treatment%22">Asthma treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Inhalers%22">Inhalers</searchLink><br /><searchLink fieldCode="DE" term="%22Immunology+of+inflammation%22">Immunology of inflammation</searchLink><br /><searchLink fieldCode="DE" term="%22Sputum+examination%22">Sputum examination</searchLink><br /><searchLink fieldCode="DE" term="%22Neutrophils%22">Neutrophils</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: BACKGROUND: Ozone exposure induces airway neutrophilia and modifies innate immune monocytic cell-surface phenotypes in healthy individuals. High-dose inhaled corticosteroids can reduce O3-induced airway inflammation, but their effect on innate immune activation is unknown. OBJECTIVES: We used a human O3 inhalation challenge model to examine the effectiveness of clinically relevant doses of inhaled corticosteroids on airway inflammation and markers of innate immune activation in healthy volunteers. METHODS: Seventeen O3-responsive subjects [> 10% increase in the percentage of polymorphonuclear leukocytes (PMNs) in sputum, PMNs per milligram vs. baseline sputum] received placebo, or either a single therapeutic dose (0.5 mg) or a high dose (2 mg) of inhaled fluticasone proprionate (FP) 1 hr before a 3-hr O3 challenge (0.25 ppm) on three separate occasions at least 2 weeks apart. Lung function, exhaled nitric oxide, sputum, and systemic biomarkers were assessed 1-5 hr after the O3 challenge. To determine the effect of FP on cellular function, we assessed sputum cells from seven subjects by flow cytometry for cell-surface marker activation. RESULTS: FP had no effect on O3-induced lung function decline. Compared with placebo, 0.5 mg and 2 mg FP reduced O3-induced sputum neutrophilia by 18% and 35%, respectively. A similar effect was observed on the airway-specific serum biomarker Clara cell protein 16 (CCP16). Furthermore, FP pretreatment significantly reduced O3-induced modification of CD11b, mCD14, CD64, CD 16, HLA-DR, and CD86 on sputum monocytes in a dose-dependent manner. CONCLUSION: This study confirmed and extended data demonstrating the protective effect of FP against O3-induced airway inflammation and immune cell activation. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1289/ehp.10981 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 799 Subjects: – SubjectFull: Physiological effects of ozone Type: general – SubjectFull: Biomarkers Type: general – SubjectFull: Adrenocortical hormones Type: general – SubjectFull: Asthma treatment Type: general – SubjectFull: Inhalers Type: general – SubjectFull: Immunology of inflammation Type: general – SubjectFull: Sputum examination Type: general – SubjectFull: Neutrophils Type: general Titles: – TitleFull: Fluticasone Propionate Protects against Ozone-Induced Airway Inflammation and Modified Immune Cell Activation Markers in Healthy Volunteers. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Alexis, Neil E. – PersonEntity: Name: NameFull: Lay, John C. – PersonEntity: Name: NameFull: Haczku, Angela – PersonEntity: Name: NameFull: Gong, Henry – PersonEntity: Name: NameFull: Linn, William – PersonEntity: Name: NameFull: Hazucha, Milan J. – PersonEntity: Name: NameFull: Harris, Brad – PersonEntity: Name: NameFull: Tal-Singer, Ruth – PersonEntity: Name: NameFull: Peden, David B. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 06 Text: Jun2008 Type: published Y: 2008 Identifiers: – Type: issn-print Value: 00916765 Numbering: – Type: volume Value: 116 – Type: issue Value: 6 Titles: – TitleFull: Environmental Health Perspectives Type: main |
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