Sputum or blood eosinophil association with clinical measures of COPD severity in the SPIROMICS cohort

BACKGROUND: Eosinophils in blood and sputum in chronic obstructive pulmonary disease (COPD) have been associated with more frequent exacerbations, lower lung function, and corticosteroid responsiveness. We hypothesized increased eosinophils are associated with a severe COPD phenotype, including exacerbation frequency, and tested whether blood eosinophils reliably predict sputum eosinophils. METHODS: Comprehensive baseline data on SPIROMICS subjects, recruited for a range of COPD severity for smokers with ≥20 pack year history, included demographics, questionnaires, clinical assessments, quantitative computed tomography (QCT), blood and induced sputum. FINDINGS: Significantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV(1) % predicted (differences: 10% pre-bronchodilator, 4·7% post-bronchodilator), QCT density measures for emphysema and air trapping, and exacerbations treated with corticosteroids (p=0·002). In contrast, stratification by mean blood eosinophils ≥200/µL (N=2499) showed that FEV(1) % predicted was significant between low and high blood subgroups, but less than observed between sputum subgroups (blood eosinophil group differences: 4·2% pre-bronchodilator, 2·7% post-bronchodilator), slightly increased airway wall thickness (0·02 mm, p=0·032), greater symptoms (p=0·037), and wheezing (p=0·018), but no evidence of association with COPD exacerbations or other indices of severity. Blood eosinophils showed weak although significant association with sputum eosinophils (ROC AUC=0·64, p<0·001), but with a high false discovery rate (72%). Elevated sputum eosinophils, with or without blood eosinophils, were associated with lower lung function. Elevated blood eosinophils only in combination with elevated sputum eosinophils were associated with COPD exacerbations. INTERPRETATION: Stratification of SPIROMICS subjects by blood eosinophils alone showed minimal clinical differences and no association with exacerbations, whereas stratification by sputum eosinophils was associated with larger phenotypic differences and COPD exacerbations. Importantly, increased blood eosinophils did not reliably predict airway eosinophils in induced sputum.