Eosinophil and T cell markers predict functional decline in COPD patients.
BACKGROUND
The major marker utilized to monitor COPD patients is forced expiratory volume in one second (FEV1). However, a single 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 (DeltaFEV1 % predicted = 4.7 +/- 7.2; N = 34) were retrospectively compared with study participants who experienced a rapid decline in lung function (DeltaFEV1 % 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.


CONCLUSIONS
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).


CONCLUSIONS
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.
D'Armiento
Jeanine M
JM
Department of Medicine, Columbia University, New York, NY, USA. jmd12@columbia.edu
Scharf
Steven M
SM
Roth
Michael D
MD
Connett
John E
JE
Ghio
Andrew
A
Sternberg
David
D
Goldin
Jonathan G
JG
Louis
Thomas A
TA
Mao
Jenny T
JT
O'Connor
George T
GT
Ramsdell
Joe W
JW
Ries
Andrew L
AL
Schluger
Neil W
NW
Sciurba
Frank C
FC
Skeans
Melissa A
MA
Voelker
Helen
H
Walter
Robert E
RE
Wendt
Christine H
CH
Weinmann
Gail G
GG
Wise
Robert A
RA
Foronjy
Robert F
RF
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D001999:Bronchoscopy; D054413:Chemokine CCL11 / Q000097:blood; D016207:Cytokines / Q000097:blood*; D018450:Disease Progression; D004804:Eosinophils / Q000276:immunology*; D005541:Forced Expiratory Volume; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000503:physiopathology; D008875:Middle Aged; D011237:Predictive Value of Tests; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D016032:Randomized Controlled Trials as Topic; D019141:Respiratory System Agents / Q000627:therapeutic use; D012189:Retrospective Studies; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D014212:Tretinoin / Q000627:therapeutic use; D014797:Vital Capacity
D015415:Biomarkers; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D016207:Cytokines; C508594:IL2 protein, human; D007376:Interleukin-2; D019141:Respiratory System Agents; D014212:Tretinoin