How is eosinophil count determined in asthma?

Determining Eosinophil Count in Asthma

Eosinophil count in asthma is determined through two primary methods: induced sputum analysis (the gold standard for airway inflammation) and peripheral blood eosinophil measurement (more practical for routine clinical use). 1

Induced Sputum Analysis

Methodology

• Sputum is induced using nebulized hypertonic saline and processed with the mucolytic dithiothreitol. 1
• The procedure requires pretreatment with short-acting beta-agonists (SABA) to prevent bronchospasm. 1
• Success rates are 80-90% in adults and somewhat lower in children; not feasible in children under 8 years. 1
• Low baseline lung function (FEV1 <1.0 L) is a relative contraindication. 1

Laboratory Processing

• The principal readout is the differential inflammatory cell count, expressed as a percentage, based on manual count of 400 inflammatory cells (eosinophils, neutrophils, macrophages, lymphocytes, and epithelial cells) on a stained cytospin preparation. 1
• Total cell count, cell viability, and squamous cell contamination must also be reported. 1
• Different processing methods (sputum plugs vs. whole sample selection) do not result in clinically important differences in differential cell counts. 1

Normal Values and Interpretation

• The upper limit of normal for sputum eosinophil differential count is 1.9%. 1
• Eosinophilic airway inflammation is defined as sputum eosinophil count >1.9%. 1
• A sputum eosinophil count <3% has 100% negative predictive value for >12% increase in FEV1 in response to inhaled corticosteroids. 1
• A halving or doubling of the sputum differential eosinophil count is considered clinically significant, with 90% sensitivity for loss of asthma control after inhaled corticosteroid withdrawal. 1

Clinical Utility

• Raised sputum eosinophil counts predict asthma exacerbations, and management strategies targeting eosinophil normalization reduce severe exacerbations by up to 60%. 1
• Sputum-guided therapy provides particular benefit in patients taking long-acting beta-agonists or those with more severe asthma. 1
• Important caveat: Induced sputum facilities are currently only available in secondary care and specialist laboratories. 1

Peripheral Blood Eosinophil Count

Measurement Approach

• Blood eosinophil count is obtained through standard complete blood count with differential. 2
• This method is more accessible than induced sputum analysis and can be performed in primary care settings. 1

Threshold Values for Clinical Decision-Making

• A blood eosinophil count ≥150 cells/μL is used to identify patients eligible for anti-IL-5 therapy. 3, 4
• Blood eosinophil count ≥300 cells/μL indicates higher likelihood of eosinophilic inflammation. 3
• Blood eosinophil count ≥400 cells/μL is a risk factor for future asthma exacerbations (adjusted rate ratio 1.31). 5
• Counts >350 cells/μL yield 88% specificity and 93% positive predictive value for exercise-induced bronchospasm. 6

Variability Considerations

• A single blood eosinophil measurement ≥150 cells/μL predicts that the average of subsequent measurements will remain ≥150 cells/μL in 85% of patients. 4
• Blood eosinophil levels between 150-299 cells/μL are least stable, with only 44% of patients remaining in the same classification over time. 7
• Nearly 50% of patients with uncontrolled asthma have eosinophil levels that traverse the 300 cells/μL threshold over time. 8
• Multiple measurements are recommended when using eosinophil counts for diagnosis and management of eosinophilic asthma, as a single measurement may not be sufficient. 7

Factors Affecting Blood Eosinophil Levels

• Nasal polyps increase eosinophil levels by 38%. 7
• Current smoking decreases eosinophil levels by 23%. 7
• Substantial seasonal variation exists, with approximately 20% difference between July and January. 7
• Age may affect counts, particularly over age 50. 1
• Time from blood collection to laboratory analysis affects results, with longer delays reducing counts and increasing variability. 7

Critical Pitfalls to Avoid

Discordance Between Measurements

• Peripheral blood eosinophil counts may not correlate with tissue eosinophilia, particularly in eosinophilic esophagitis where tissue biopsy remains the gold standard. 2
• Symptoms and eosinophilic inflammation can be dissociated in some asthma phenotypes, with significant discordance seen in secondary care patients. 2
• In primary care, most patients show concordance between symptoms and eosinophilic airway inflammation, but discordance is common in secondary care referrals. 1

Timing Considerations

• Eosinophil counts respond rapidly to corticosteroids (effects may be seen as early as 6 hours), so timing relative to treatment is critical. 1
• The dose-response curve for inhaled corticosteroids plateaus at low doses (approximately 200 mcg/day beclomethasone equivalent). 1

When to Use Each Method

• Use induced sputum analysis when available in specialist settings for precise assessment of airway inflammation and to guide corticosteroid therapy. 1
• Use peripheral blood eosinophil count for routine monitoring, determining eligibility for biologic therapies, and predicting exacerbation risk. 3, 5
• Obtain multiple blood eosinophil measurements over time rather than relying on a single value, especially when counts fall in the 150-299 cells/μL range. 8, 7