What is the utility of measuring sputum eosinophils in patients with asthma or suspected asthma, particularly those with severe or uncontrolled symptoms?

Utility of Sputum Eosinophils in Asthma Management

Sputum eosinophil measurement is a clinically valuable tool that provides critical information about corticosteroid responsiveness and future exacerbation risk, particularly in patients with moderate to severe asthma, and should be used in specialist settings where technical expertise is available. 1

Primary Clinical Applications

Predicting Corticosteroid Responsiveness

• Sputum eosinophil count <3% has 100% negative predictive value for significant FEV1 improvement (>12%) with inhaled corticosteroids, making it highly useful for identifying patients unlikely to benefit from ICS therapy 1
• Eosinophilic airway inflammation (sputum eosinophils >1.9-3%) consistently predicts beneficial short- and long-term response to corticosteroid therapy regardless of clinical context 1
• The presence of sputum eosinophilia identifies corticosteroid-responsive disease even in patients with chronic cough without asthma 2

Predicting and Preventing Exacerbations

• A raised sputum eosinophil count predicts asthma exacerbations with 90% sensitivity when corticosteroids are withdrawn or reduced 1
• Management strategies targeting normalization of sputum eosinophil counts reduce severe asthma exacerbations by up to 60%, with particular benefit in patients taking long-acting beta-agonists or those with more severe asthma 1
• Patients with persistently elevated sputum eosinophils demonstrate severe airflow obstruction, frequent exacerbations, and high mucus plug scores 3

Cost-Effectiveness and Clinical Setting

Induced sputum analysis has been proven cost-efficient in specialist settings for patients with moderate to severe asthma, where it augments clinical assessment for both diagnosis and treatment decisions 1

The technique requires technical expertise for sputum induction and processing, limiting its widespread use to specialized centers 1

Critical Clinical Insights

Dissociation from Clinical Parameters

• Significant dissociation exists between eosinophilic airway inflammation and symptoms/airway function in some asthma phenotypes, particularly in patients referred to secondary care 1
• Clinical variables alone cannot predict the presence or absence of airway eosinophilia, making objective measurement essential 4
• Sputum eosinophils provide complementary data to clinical and functional indices, as they do not accurately reflect current symptom severity or FEV1 in chronic stable patients 5

Blood vs. Sputum Eosinophils

• Blood eosinophil counts frequently miss airway eosinophilic inflammation: high sputum eosinophils occur in 27% of patients with blood eosinophils <150 cells/μL and 42% with blood eosinophils 150-299 cells/μL 3
• Sputum eosinophil peroxidase (EPX) is a more sensitive biomarker of airway eosinophilic inflammation than sputum eosinophil counts alone 3
• The correlation between blood and sputum eosinophils is modest, emphasizing that systemic markers do not reliably reflect airway inflammation 3

Treatment Response Monitoring

Corticosteroid Effects

• Sputum eosinophil counts decrease 2- to 7-fold with corticosteroid treatment, with effects potentially visible as early as 6 hours 1
• A halving or doubling of sputum differential eosinophil count is considered clinically significant 1
• Among asthmatics not using inhaled corticosteroids, sputum eosinophils are significantly higher (6.5% vs 0.5%) compared to those on treatment 4

Biologic Therapy Monitoring

• In patients starting mepolizumab, serum eosinophils normalize in 96% but sputum eosinophils normalize in only 49%, indicating persistent airway inflammation despite systemic control 3
• This finding emphasizes that sputum measurement provides unique information about airway-specific treatment response not captured by blood eosinophils 3

Practical Implementation Algorithm

When to Measure Sputum Eosinophils

1. Patients with moderate to severe asthma being evaluated in specialist settings 1
2. Before initiating or escalating corticosteroid therapy to predict responsiveness 1
3. Patients with persistent symptoms despite treatment to identify inflammation-predominant vs. symptom-predominant phenotypes 1
4. When considering corticosteroid dose reduction to assess ongoing inflammation risk 1
5. Patients with chronic cough without clear asthma diagnosis to identify eosinophilic bronchitis 2, 4

Interpretation Thresholds

• Normal range: ≤1.9-2.75% eosinophils 1, 4
• Eosinophilic bronchitis: >2.75-3% eosinophils 1, 4
• Clinically significant change: halving or doubling of baseline count 1

Common Pitfalls to Avoid

• Do not rely solely on clinical assessment or blood eosinophils to determine airway eosinophilic inflammation, as significant discordance exists between these measures and sputum findings 1, 4, 3
• Do not assume symptom severity correlates with eosinophilic inflammation, particularly in secondary care populations where dissociation is common 1
• Do not use sputum induction in primary care settings without appropriate technical expertise and resources, as the procedure requires specialized training 1
• Do not assume normalized blood eosinophils on biologic therapy indicate normalized airway inflammation, as sputum eosinophils may remain elevated 3

Pediatric Considerations

Successful sputum induction in children is limited to those 8 years and older, with success rates around 60-70% in academic settings 1

Serial sputum assessment may be problematic in children, as many are unwilling to undergo repeat inductions during follow-up visits 1