How should I diagnose non‑asthmatic eosinophilic bronchitis in a 35‑year‑old woman with a 30‑day productive cough?

Diagnosing Non-Asthmatic Eosinophilic Bronchitis

Diagnose non-asthmatic eosinophilic bronchitis by documenting sputum eosinophilia ≥3% on induced sputum analysis after excluding other causes of chronic cough through spirometry showing normal airflow and methacholine challenge testing demonstrating normal airway responsiveness (PC20 >16 mg/mL). 1

Diagnostic Criteria

Non-asthmatic eosinophilic bronchitis requires all of the following features 1:

• Chronic cough (≥8 weeks duration, though your patient's 30-day cough is approaching this threshold) 1
• No symptoms or objective evidence of variable airflow obstruction (normal spirometry) 1
• Normal airway hyperresponsiveness on methacholine challenge (PC20 >16 mg/mL) 1
• Sputum eosinophilia ≥3% of non-squamous cells 1

Step-by-Step Diagnostic Algorithm

Step 1: Exclude Other Causes of Chronic Cough

Before pursuing sputum analysis, perform 1:

• Clinical assessment: Look for post-nasal drip symptoms, gastroesophageal reflux symptoms, or medication-induced cough (ACE inhibitors)
• Chest radiograph: Rule out structural lung disease, malignancy, or infection
• Spirometry with bronchodilator: Must show normal FEV1/FVC ratio and no significant bronchodilator response (excludes asthma) 1

Step 2: Perform Methacholine Challenge Testing

This is essential to differentiate non-asthmatic eosinophilic bronchitis from cough-variant asthma 1:

• Normal result (PC20 >16 mg/mL) supports non-asthmatic eosinophilic bronchitis
• Positive result (PC20 ≤16 mg/mL) indicates cough-variant asthma instead
• The absence of airway hyperresponsiveness is the key distinguishing feature from asthma 1

Step 3: Document Sputum Eosinophilia

Induced sputum analysis is the gold standard diagnostic test 1, 2, 3:

Sputum induction technique 1:

• Premedicate with a short-acting bronchodilator
• Patient inhales hypertonic saline (3%, 4%, then 5%) for 5 minutes each via ultrasonic nebulizer
• Expectorated sputum is processed with mucolytic agent, filtered through 48-μm mesh, and centrifuged
• Count 400 non-squamous cells on cytospin preparation
• ≥3% eosinophils is diagnostic (normal is <1.1%) 1

Important technical considerations 1:

• Requires same-day processing for accurate cell counts and viability
• Safe and repeatable procedure
• May also identify neutrophilia from bacterial/viral bronchitis

Alternative if sputum induction unavailable or unsuccessful 1:

• Bronchoscopy with bronchial wash fluid provides similar information to induced sputum 1

Key Distinguishing Features from Related Conditions

The ACCP guidelines provide clear differentiation 1:

Feature	Non-Asthmatic Eosinophilic Bronchitis	Cough-Variant Asthma	Classic Asthma
Airway hyperresponsiveness	Absent	Present	Present
Bronchodilator response	Absent	Good	Good
Spirometry	Normal	Normal	Abnormal
Sputum eosinophilia	Always present	Usually present	Usually present

Common Pitfalls to Avoid

Do not rely on clinical features alone 1:

• The nature and timing of cough provides limited diagnostic help
• Physical examination is typically normal
• Upper airway symptoms may be present but are non-specific

Always consider multiple causes 1:

• Non-asthmatic eosinophilic bronchitis accounts for 10-30% of chronic cough cases referred for specialist evaluation 1
• Multiple causes often coexist, so continue investigating even if another cause is identified
• Consider non-asthmatic eosinophilic bronchitis if there is no response or only partial response to treatment of another identified cause 1

Exhaled nitric oxide has limitations 1:

• While elevated in some cases, it is not sufficiently validated as a standalone diagnostic test for non-asthmatic eosinophilic bronchitis
• Sputum eosinophil count remains the definitive test 1, 2

Special Considerations for Your 35-Year-Old Patient

The 30-day duration is shorter than the typical 8-week definition of chronic cough 1:

• Consider treating acute/subacute causes first (post-viral cough, acute bronchitis)
• If cough persists beyond 8 weeks, proceed with full diagnostic workup for non-asthmatic eosinophilic bronchitis

Productive cough is consistent with the diagnosis 1:

• Non-asthmatic eosinophilic bronchitis often presents with cough and sputum production
• The productive nature allows for spontaneous sputum collection if available, though induced sputum is more reliable 1, 4

Consider occupational or allergen exposure 1:

• Ask specifically about workplace exposures to sensitizers
• Inquire about new environmental allergen exposures
• These may be treatable causes requiring allergen avoidance 1, 5