Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood.
BACKGROUND
Airway eosinophilic inflammation is a characteristic feature of asthma. This can be assessed directly by measurement of eosinophils and eosinophilic cationic protein (ECP) in sputum or indirectly by measurement of the same markers in blood. We investigated the performance of these markers of airway eosinophilic inflammation in a population of patients with asthma compared with control subjects and the extent to which the markers differed.


METHODS
In a cross-sectional study, subject characteristics were documented on day 1 and induced sputum and blood samples were obtained on day 2. Nineteen patients with asthma and 20 control subjects (10 healthy subjects and 10 smokers with nonobstructive bronchitis) were consecutively enrolled in the study. Sputum (selected from saliva) and blood samples were processed by persons blind to the clinical details. Results are presented as median values (minimum-maximum); differences were measured by Mann-Whitney U test. The accuracy of the tests (sensitivity and specificity) was measured by plotting the data in receiver-operating characteristic (ROC) curves and comparing the areas under the curve for each marker.


RESULTS
Patients with asthma in comparison with control subjects had a higher proportion of sputum eosinophils (5.2% [0.2% to 93%] vs 0.3% [0% to 1.7%], p < 0.001), higher numbers of blood eosinophils (350.0 x 10(6)/L [144.0 to 1520.0 x 10(6)/L] vs 155.0 x 10(6)/L [34.0 to 426.0 x 10(6)/L], p = 0.003), and higher levels of ECP in sputum (1040.0 micrograms/L [76.8 to 32,000.0 micrograms/L] vs 455.3 micrograms/L [54.4 to 1280.0 micrograms/L], p = 0.001) but not in serum (25.0 micrograms/L [5.6 to 52.4 micrograms/L] vs 16.5 micrograms/L [3.3 to 36.0 micrograms/L], p = 0.08). Markers of airway inflammation in induced sputum and blood samples were correlated with clinical and physiologic variables. The area under the ROC curve showed that eosinophils in sputum (0.90) are significantly more accurate markers than blood eosinophils (0.72) and serum ECP (0.67) (p = 0.02). Although the area under the ROC curve for sputum ECP was greater than those for blood eosinophils and serum ECP, the differences could have occurred by chance (p > or = 0.1).


CONCLUSIONS
We conclude that the proportion of eosinophils in sputum is a more accurate marker of asthmatic airway inflammation than the proportions of blood eosinophils or serum ECP.
Pizzichini
E
E
Department of Medicine, St. Joseph's Hospital, Hamilton, Ontario, Canada.
Pizzichini
M M
MM
Efthimiadis
A
A
Dolovich
J
J
Hargreave
F E
FE
D000328:Adult; D000368:Aged; D001249:Asthma / Q000175:diagnosis*; D015415:Biomarkers / Q000032:analysis; D001798:Blood Proteins / Q000032:analysis*; D001991:Bronchitis / Q000175:diagnosis; D003430:Cross-Sectional Studies; D047091:Eosinophil Granule Proteins; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012260:Ribonucleases; D012680:Sensitivity and Specificity; D012907:Smoking / Q000378:metabolism; D013183:Sputum / Q000737:chemistry / Q000166:cytology*
D015415:Biomarkers; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018836:Inflammation Mediators; D012260:Ribonucleases