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Eosinophil and T cell markers predict functional decline in COPD patients

Jeanine M D'Armiento1 email, Steven M Scharf2 email, Michael D Roth3 email, John E Connett4 email, Andrew Ghio5 email, David Sternberg1 email, Jonathan G Goldin3 email, Thomas A Louis6 email, Jenny T Mao3 email, George T O'Connor7 email, Joe W Ramsdell8 email, Andrew L Ries8 email, Neil W Schluger1 email, Frank C Sciurba9 email, Melissa A Skeans3 email, Helen Voelker3 email, Robert E Walter6 email, Christine H Wendt3 email, Gail G Weinmann10 email, Robert A Wise5 email and Robert F Foronjy1 email

Departments of Medicine and Surgery, Columbia University, New York, USA

Department of Medicine, University of Maryland, Baltimore, USA

Departments of Medicine and Radiology, University of California, Los Angeles, USA

Departments of Medicine and Biostatistics/CCBR, University of Minnesota, Twin Cities, USA

National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, USA

Department of Medicine, Johns Hopkins University, Baltimore, USA

Department of Medicine, Boston University, Boston, USA

Department of Medicine, University of California, San Diego, San Diego, USA

Department of Medicine, University of Pittsburgh, Pittsburgh, USA

10  National Institutes of Health, Bethesda, MD, USA

author email corresponding author email

Respiratory Research 2009, 10:113doi:10.1186/1465-9921-10-113

Published: 19 November 2009

Abstract

Background

The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, asingle measurement of FEV1 cannot reliably predict subsequent decline. Recent studies indicate that T lymphocytes and eosinophils are important determinants of disease stability in COPD. We therefore measured cytokine levels in the lung lavage fluid and plasma of COPD patients in order to determine if the levels of T cell or eosinophil related cytokines were predictive of the future course of the disease.

Methods

Baseline lung lavage and plasma samples were collected from COPD subjects with moderately severe airway obstruction and emphysematous changes on chest CT. The study participants were former smokers who had not had a disease exacerbation within the past six months or used steroids within the past two months. Those subjects who demonstrated stable disease over the following six months (ΔFEV1 % predicted = 4.7 ± 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (ΔFEV1 % predicted = -16.0 ± 6.0; N = 16) during the same time period and with normal controls (N = 11). Plasma and lung lavage cytokines were measured from clinical samples using the Luminex multiplex kit which enabled the simultaneous measurement of several T cell and eosinophil related cytokines.

Results and Discussion

Stable COPD participants had significantly higher plasma IL-2 levels compared to participants with rapidly progressive COPD (p = 0.04). In contrast, plasma eotaxin-1 levels were significantly lower in stable COPD subjects compared to normal controls (p < 0.03). In addition, lung lavage eotaxin-1 levels were significantly higher in rapidly progressive COPD participants compared to both normal controls (p < 0.02) and stable COPD participants (p < 0.05).

Conclusion

These findings indicate that IL-2 and eotaxin-1 levels may be important markers of disease stability in advanced emphysema patients. Prospective studies will need to confirm whether measuring IL-2 or eotaxin-1 can identify patients at risk for rapid disease progression.


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