What is the significance of an elevated percentage of eosinophils in the Differential Leukocyte Count (DLC) for asthma management in pediatric patients?

Elevated Eosinophils in Pediatric Asthma: Clinical Significance

An elevated percentage of eosinophils in the differential leukocyte count (DLC) in children with asthma indicates type 2 (T2-high) inflammatory phenotype, predicts corticosteroid responsiveness, and identifies patients at higher risk for asthma exacerbations who may benefit from intensified anti-inflammatory therapy.

Understanding Eosinophilic Inflammation in Pediatric Asthma

Prevalence and Phenotype Significance

• T2-high asthma endotype, characterized by eosinophilic airway inflammation and allergic sensitization driven by IgE and IL-4, IL-5, and IL-13, is more commonly detected in asthmatic children compared to adults 1
• Blood eosinophilia in pediatric asthma typically represents modest elevations (2-fold increases), though the relationship between peripheral blood eosinophils and tissue eosinophilia is not always consistent 2
• Peripheral blood eosinophil counts may not correlate with tissue eosinophilia, as inflammation can be localized to airways without systemic elevation 2, 3

Predictive Value for Treatment Response

Eosinophil counts strongly predict corticosteroid responsiveness across multiple measures:

• Sputum eosinophil counts provide compelling evidence of beneficial short- and long-term response to corticosteroid therapy, with a sputum eosinophil count <3% having 100% negative predictive value for significant FEV1 improvement with inhaled corticosteroids (ICS) 1
• Raised sputum eosinophil counts predict asthma exacerbations with 90% sensitivity when corticosteroids are withdrawn 2, 3
• Management strategies targeting eosinophil normalization reduce severe asthma exacerbations by up to 60%, with particular benefit in patients with more severe asthma 1, 3
• Eosinophil counts decrease 2- to 7-fold with corticosteroid treatment, with effects potentially visible as early as 6 hours 2

Clinical Implications for Asthma Management

Use elevated eosinophils to guide the following treatment decisions:

• Initiation of ICS therapy: Elevated eosinophils indicate likely benefit from corticosteroid treatment, as eosinophilic inflammation responds robustly to these medications 1, 2
• Intensification of therapy: Children with persistent eosinophilia despite standard ICS therapy are at increased risk for exacerbations and may require step-up treatment including biologics targeting IL-5 or IL-5α receptor 4, 5
• Monitoring treatment adequacy: A decrease in peripheral blood eosinophil counts ranging from 9% to 15% is expected with effective ICS therapy in children aged 2 years and older 6

Practical Measurement Approaches

Blood Eosinophil Count (Most Accessible)

• Obtained through standard complete blood count with differential, accessible in primary care settings 7
• More practical than induced sputum in pediatric populations where sputum induction success is limited to children 8 years and older with only 60-70% success rates 1
• Age may affect blood eosinophil counts, particularly over age 50, though this is less relevant in pediatric populations 7

Induced Sputum Analysis (Gold Standard)

• The American Thoracic Society recommends induced sputum as the gold standard for airway inflammation assessment, with upper limit of normal for sputum eosinophil differential count at 1.9% 3, 7
• Requires specialized equipment and expertise, with success rates around 60-70% in children 8 years and older in academic settings 1
• Many children are unwilling to undergo repeat sputum inductions during follow-up visits, limiting serial assessment 1
• A halving or doubling of sputum differential eosinophil count is considered clinically significant 7

Fractional Exhaled Nitric Oxide (FeNO) as Surrogate

• FeNO measurements serve as a surrogate marker for eosinophilic airway inflammation and may help evaluate potential for corticosteroid response 1
• Low FeNO values (<20 ppb in children) may be particularly valuable in determining that ongoing airway symptoms are unlikely due to eosinophilic inflammation 1
• Reliable measurement using single-breath online technique is limited to children 5 years and older 1

Critical Pitfalls to Avoid

Important caveats when interpreting eosinophil counts:

• Dissociation between inflammation and symptoms: There is accumulating evidence of important dissociation between eosinophilic airway inflammation and symptoms/disordered airway function in some asthma phenotypes 1
• Timing relative to corticosteroid use: Eosinophil counts respond rapidly to corticosteroids, so timing of measurement relative to treatment is critical for accurate interpretation 2, 7
• Peripheral versus tissue eosinophilia: Blood eosinophil counts may not reflect airway tissue eosinophilia, particularly in conditions like eosinophilic esophagitis where tissue biopsy remains the gold standard 2, 3, 7
• Non-eosinophilic responders: Some children with difficult asthma may benefit clinically from high-dose systemic corticosteroids even in the absence of sputum eosinophilia, suggesting other inflammatory mechanisms 8
• Adherence issues: In patients with elevated blood eosinophils (>400 cells/μL), poor adherence to ICS therapy is common (83% not fully adherent), and adherence alone may not prevent exacerbations in this population 5

Treatment Algorithm Based on Eosinophil Status

For children with elevated peripheral blood eosinophils:

1. Confirm asthma diagnosis and assess baseline eosinophil count through standard DLC 1
2. Initiate or optimize ICS therapy as first-line treatment, expecting 9-15% reduction in eosinophil counts with effective therapy 6
3. Monitor response at 4-8 weeks, assessing both clinical control and eosinophil count reduction 1
4. If persistent eosinophilia with poor control: Consider step-up to combination ICS/LABA therapy 9
5. If severe asthma with persistent eosinophilia despite maximal inhaled therapy: Consider biologics targeting IL-5 or IL-5α receptor (mepolizumab, reslizumab, benralizumab), which reduce exacerbations by approximately 50% 4
6. Use sputum eosinophil counts when available in specialist settings for precise assessment, particularly in moderate-to-severe asthma where cost-effectiveness has been demonstrated 1

For children with low/normal eosinophils and persistent symptoms:

• Consider non-eosinophilic asthma phenotypes (neutrophilic or paucigranulocytic), which are less responsive to corticosteroids 3
• Evaluate for alternative diagnoses or comorbidities contributing to symptoms 1
• Assess adherence to prescribed therapy before escalating treatment 5