Sputum eosinophil count may predict severity of COPD in smokers, research suggests

- Blood eosinophil count alone not predictive in SPIROMICS cohort
By Dr Deepu

Investigators found that “sputum eosinophil count proved to be a better biomarker of chronic obstructive pulmonary disease (COPD) severity and exacerbations than blood eosinophil count alone in a study involving a large group of smokers with a broad range of airflow obstruction severities.” The investigators found, “in the analysis...blood eosinophil count as a single biomarker was not predictive of sputum eosinophils and was not associated with disease severity or exacerbations unless combined with sputum count.” But, “increased sputum eosinophil inflammation...was found to be associated with more severe COPD, decreased lung function, worse emphysema and air trapping, and a greater likelihood of exacerbations.” The findings were published in The Lancet Respiratory Medicine

Patients enrolled in SPIROMICS had a smoking history of at least 20 pack-years and were recruited from six clinical sites and subsites in the U.S. between November 2010 and spring 2015. All had complete baseline blood cell counts, and a subset had acceptable sputum counts.

A total of 2,499 participants with available blood counts were stratified by mean blood eosinophil count: 1,262 patients with low (<200 cells per μL) and 1,237 with high (≥200 cells per μL) blood eosinophil counts.

A total of 827 patients were eligible for stratification by mean sputum eosinophil percentage including 656 with low (<1.25%) and 171 with high (≥1.25%) sputum eosinophil percentages. Analyses were also conducted involving blood eosinophil cutoffs of 300 cells/μL and sputum eosinophil cutoffs of 2%.

The high sputum eosinophil group had significantly lower median forced expiratory volume in 1 second (FEV)₁ percentage predicted than the low sputum eosinophil group, both before (65.7% [IQR 51.8-81.3] versus 75.7% [59.3-90.2], P<0·0001) and after (77.3% [63.1-88·5] versus 82.9% [67.8-95.9], P=0.001) bronchodilation.

Qualitative computed tomography (CT) density measures for emphysema and air trapping were significantly higher in the high sputum eosinophil group than in the low sputum eosinophil group and exacerbations requiring corticosteroids treatment were more common in the high versus low sputum eosinophil group (P=0.002).
The main findings of the study are:

FEV₁ percentage predicted was significantly different between low and high blood eosinophil groups, but differences were less than those observed between the sputum groups

The high blood eosinophil group had slightly increased airway wall thickness (0.02 mm difference, P=0·032), higher St George Respiratory Questionnaire symptom scores (P=0.037), and increased wheezing (P=0.018, but no evidence of an association with COPD exacerbations (P=0.35) or the other indices of COPD severity, such as emphysema measured by CT density, COPD assessment test scores, BMI, airflow Obstruction, Dyspnea, and Exercise index, or Global Initiative for Chronic Obstructive Lung Disease stage

Blood eosinophil counts showed a weak but significant association with sputum eosinophil counts (receiver operating characteristic area under the curve of 0.64, P<0.0001), but with a high false-discovery rate of 72%

With the higher blood eosinophil cutoff of 300 cells/μL, no significant differences were seen between the high and low count groups. But at the higher 2% sputum eosinophil cutoff, significant differences were seen between the low and high groups for all categories of COPD exacerbations.

The ECLIPSE study reported that 1,483 patients stratified by blood eosinophil counts did not have different numbers of COPD exacerbations in the previous year. Researchers noted that higher blood eosinophils are not associated with COPD exacerbations except when combined with increased sputum eosinophils or with other characteristics, such as a previous history of exacerbations. In the SPIROMICS cohort, higher sputum eosinophil counts alone are associated with exacerbations even in mild to moderate COPD