alexa Evidence of Elevated CXCR2 Agonists in Stable Outpatients with Cystic Fibrosis Compared with Healthy Controls
ISSN: 2161-105X

Journal of Pulmonary & Respiratory Medicine
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Research Article

Evidence of Elevated CXCR2 Agonists in Stable Outpatients with Cystic Fibrosis Compared with Healthy Controls

Lipson David A1,2, Holsclaw Douglas2, Imbesi Giovanna2, Ferrin Marianne2, Sims Michael2, Miller Sam3, Tal-Singer Ruth1, and Hadjiliadis Denis2*

1Respiratory Discovery Medicine, GlaxoSmithKline, King of Prussia, PA, USA

2Pulmonary, Allergy & Critical Care Division, University of Pennsylvania Medical Center, Philadelphia, PA, USA

3Quantitative Sciences, Discovery Statistics, GlaxoSmithKline, Cambridge, UK

*Corresponding Author:
Denis Hadjiliadis, MD, MHS, FRCP(C)
Paul F Harron Jr Associate Professor of Medicine Pulmonary
Allergy and Critical Care, University of Pennsylvania
Philadelphia, PA, 19104, USA
Tel: 215-615-3871
Fax: 215-614-0869
E-mail: [email protected] or [email protected]

Received date: May 09, 2013; Accepted date: June 18, 2013; Published date: June 20, 2013

Citation: Lipson David A, Douglas H, Giovanna I, Marianne F, Michael S (2013) Evidence of Elevated CXCR2 Agonists in Stable Outpatients with Cystic Fibrosis Compared with Healthy Controls. J Pulm Respir Med 3:149. doi: 10.4172/2161-105X.1000149

Copyright: © 2013 Lipson David A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Introduction: Recruitment and activation of inflammatory cells contributes to the pathophysiology of Cystic Fibrosis (CF). Recruitment is initiated, in part, by engagement of the CXCR2 receptor on neutrophils and other inflammatory cells.

Materials and Methods: Levels of CXCR2 agonists (CXCL 1, 3, 5, 7, 8), and systemic biomarkers of inflammation (fibrinogen, CC-16, SP-D, IL-1β, and MMP-9) were measured in the serum of stable outpatients with cystic fibrosis compared to normal healthy age-, gender, and racially-matched non-smoking control subjects. Secondary objectives included characterization of pulmonary function assessed by spirometry, Impulse Oscillometry (IOS), R5-R15 peripheral resistance, R5 total resistance and R25 large airway resistance; frequency dependent reactance as indicators of reactive capacitance properties of the lung (X5, resonant frequency, Fres, AX) in patients with CF compared with controls. Health outcomes scores in patients with CF were assessed using the Cystic Fibrosis Questionnaire.

Population: Single center, prospective, two visit study. 48 subjects were enrolled. Forty-two subjects (28 patients with CF and 14 healthy controls matched 2:1 (age, gender, and race) were evaluable.

Results: Blood fibrinogen levels in CF patients were significantly elevated compared with controls (3.9 g/L vs. 3.0 g/L [p=0.0004]); similar differences were seen in levels of CXCL8 (CF patients=10.2 pg/mL and controls=5.9 pg/mL [p=0.0065]). A trend was noted for CC-16, CXCL1, and SP-D. As expected, lung functions assessed by spirometry and IOS values were significantly different in the patient population compared to the control group. Mean FEV1 and mean reactance were 2.4L (67% predicted) vs. 3.5L (99% predicted) and 0.174 kPa/(L/sec) vs. –0.085 kPa/(L/sec) in CF patients vs, controls, respectively(p=0.0002 and p<0.0001)). No age or gender trends were noted among CF patients or controls.

Conclusions: The study demonstrated elevation of CXCR2 agonists in stable patients with CF. We also confirmed the potential utility of IOS, an effort-independent lung function test. Finally, the study suggests that subject matching for age and gender may not be necessary in future CF trials assessing these biomarkers.

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