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.
Authors:	Alexis, Neil E.^1,2 Neil_Alexis@med.unc.edu, Lay, John C.¹, Haczku, Angela³, Gong, Henry^4,5, Linn, William^4,5, 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]
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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]
ISSN:	00916765
DOI:	10.1289/ehp.10981