Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort

Abstract

BackgroundEosinophils 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.MethodsComprehensive 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.FindingsSignificantly, stratification by mean sputum eosinophils ≥1·25% (N=827) was associated with reduced FEV1 % 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 FEV1 % 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.InterpretationStratification 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.

Blood eosinophils could be useful as a biomarker in chronic obstructive pulmonary disease exacerbations

“…The BEC in our population is at a medium‐low level compared with that mentioned in the literature by other authors who use the same cut‐off points. More than one‐third (39.1%) of our patients have a BEC greater than 200, which is lower than the 49.4% mentioned by Hastie et al, as well as the 63.7% of the patients by Disantoestefano . Using the 300 cells/µL cut‐off point, 22.1% are equal or greater, similar to that referred to by Watz or Roche, but lower than other populations where these values increase between 32.5% and 41.4% .…”

“…In a recent study with a Spanish population, in the distribution of the BEC in relation to the severity of COPD, a similar BEC was observed for any level of severity of COPD . In another study with patients of the SPIROMICS cohort, the BEC was not associated with the severity of the COPD …”

“…In a recent meta‐analysis, Ho et al did not observe any differences in the incidence of exacerbations with respect to the BEC, but with a higher BEC the incidence was increased in the subgroup of stable patients who did not have any exacerbations in the previous 12 months . In a publication of the SPIROMICS cohort, the incidence of exacerbations does not change with the BEC …”

“…High levels of blood eosinophil counts (BEC) were observed in different studies. Data from the National Health and Nutrition Examination Survey (NHANES) showed that 70% of the individuals included had a BEC greater than 2%, although this percentage is different in other populations …”

Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

“…12,21–25 In this investigation, serum IgE was associated with asthma/COPD overlap but did not achieve significance after bonferroni adjustment for multiple comparisons. We did observe a significant association between serum levels of the Th-2 cytokine IL-4 and this outcome.…”