ATS Guidelines on Eosinophil Cut-offs in Asthma
The American Thoracic Society defines eosinophilic airway inflammation as a sputum eosinophil count >1.9%, not a peripheral blood differential leukocyte count (DLC) cut-off. 1
Understanding the Distinction: Sputum vs Blood Eosinophils
The ATS guidelines specifically address induced sputum analysis as the gold standard for assessing airway inflammation in asthma, not peripheral blood eosinophil counts from a standard DLC. 1 This is a critical distinction that is often misunderstood in clinical practice.
Sputum Eosinophil Count (ATS Recommendation)
The upper limit of normal for sputum eosinophil differential count is 1.9%, with eosinophilic airway inflammation defined as >1.9% eosinophils in induced sputum. 1
Induced sputum analysis requires nebulized hypertonic saline with pretreatment using short-acting beta-agonists, and the differential count is based on manual counting of 400 inflammatory cells on a stained cytospin preparation. 1
A halving or doubling of the sputum differential eosinophil count is considered clinically significant, with 90% sensitivity for predicting loss of asthma control after inhaled corticosteroid withdrawal. 1
Raised sputum eosinophil counts predict asthma exacerbations, and management strategies targeting eosinophil normalization reduce severe exacerbations by up to 60%. 1
Peripheral Blood Eosinophil Count (Not ATS-Specified for Diagnosis)
While the ATS does not specify a DLC cut-off for asthma diagnosis, peripheral blood eosinophil reference ranges exist:
The upper limit of normal for blood eosinophils is 0.45 × 10⁹/L (450 cells/μL or approximately 4-5% of total white blood cells). 2
In pediatric asthma exacerbations, research suggests a blood eosinophil count ≥298 cells/µL is associated with more severe disease requiring hospitalization. 3
Blood eosinophil count ≥0.450 × 10⁹ cells/L in infants hospitalized for wheezing confers a 2.9-fold increased risk of persistent childhood asthma. 4
Important Clinical Caveats
Peripheral blood eosinophil counts may not correlate with tissue eosinophilia, making them less reliable than induced sputum for assessing airway inflammation. 1 This is particularly problematic because:
Eosinophil counts respond rapidly to corticosteroids, so timing relative to treatment is critical. 1
In children with asthma, sputum inflammatory phenotypes are highly variable and not stable over time—63% of children demonstrated two or more phenotypes over one year, and 41% switched between eosinophilic and non-eosinophilic classifications. 5
Even during stable phases, 41% of children with asthma demonstrated a change in sputum inflammatory phenotype after 8 weeks. 6
Practical Recommendations
Use induced sputum analysis when available in specialist settings for precise assessment of airway inflammation and to guide corticosteroid therapy, applying the ATS cut-off of >1.9% eosinophils. 1
If only peripheral blood eosinophil counts are available (standard DLC), recognize that values >450 cells/μL (or >4-5%) are above the normal range, but this does not directly correspond to the ATS sputum-based diagnostic criteria. 2
Age correction is necessary when interpreting differential counts in patients over 50 years, as physiologic increases can be misinterpreted as pathologic. 7