What is the appropriate diagnostic and treatment approach for a patient presenting with eosinophilia, chronic cough, and pharyngitis?

Diagnostic and Treatment Approach for Eosinophilia with Chronic Cough and Pharyngitis

Initial Diagnostic Workup

The most critical first step is obtaining chest radiograph, spirometry with bronchodilator response, and methacholine challenge testing to distinguish between nonasthmatic eosinophilic bronchitis (NAEB), asthma, and other causes of chronic cough. 1

Essential Pulmonary Function Testing

• Spirometry with bronchodilator response is mandatory to differentiate NAEB from cough-variant asthma—normal spirometry without reversibility supports NAEB diagnosis 1
• Methacholine challenge test with provocative concentration >16 mg/mL excludes asthma and strongly supports NAEB 1
• Chest radiograph rules out structural lung disease and infiltrates that might suggest eosinophilic pneumonia 1

Confirming Eosinophilic Airway Inflammation

Induced sputum analysis is the gold standard diagnostic test, with ≥3% eosinophils confirming eosinophilic bronchitis. 1, 2

• The procedure involves inhaling hypertonic saline (3%, 4%, 5%) sequentially for 5 minutes each via ultrasonic nebulizer after bronchodilator premedication 2
• A differential cell count of 400 nonsquamous cells from cytospin preparation is required 2
• If sputum induction is unavailable or unsuccessful, bronchoscopy with bronchoalveolar lavage showing >25% eosinophils provides equivalent diagnostic information 1, 3

Excluding Secondary Causes of Eosinophilia

Before diagnosing primary eosinophilic bronchitis, you must systematically exclude:

• Parasitic infections (particularly if travel history to endemic areas) 3, 4
• Drug reactions (review all medications including over-the-counter) 3
• ANCA-associated vasculitis (obtain ANCA testing) 3
• Allergic bronchopulmonary aspergillosis (serum IgE, Aspergillus-specific IgE) 3
• Hematologic disorders including chronic eosinophilic leukemia—requires peripheral blood smear, flow cytometry, and molecular testing for PDGFRA/PDGFRB/FGFR1 rearrangements if absolute eosinophil count >1.5 × 10⁹/L 4, 5

Addressing the Pharyngitis Component

The pharyngitis likely represents upper airway cough syndrome (UACS), which is the most common single cause of chronic cough and frequently coexists with eosinophilic bronchitis. 6

• UACS can be completely "silent" without nasal symptoms, presenting only as throat clearing and pharyngeal irritation 6
• Gastroesophageal reflux disease (GERD) should be strongly considered as it causes laryngeal inflammation and commonly coexists with eosinophilic airway disease—up to 75% of GERD-induced cough patients have no heartburn 6, 1

Treatment Algorithm

First-Line Therapy for Confirmed NAEB

Inhaled corticosteroids are the definitive first-line treatment, with budesonide 400 μg twice daily for 4 weeks as the evidence-based regimen. 1, 7

• Expected response time is within 4 weeks, with complete cough resolution potentially requiring up to 8 weeks 2, 7
• Repeat induced sputum analysis at 4 weeks confirms reduction in eosinophil count (from ~17% to <2% in responders) 7
• A critical pitfall: beclomethasone dipropionate may paradoxically worsen cough due to dispersant components—switch to alternative inhaled corticosteroid formulations if this occurs 2

Concurrent GERD Management

Empiric proton pump inhibitor therapy should be initiated simultaneously for potential GERD contribution to pharyngitis and cough. 1, 6

• Minimum treatment duration is 8-12 weeks for extraesophageal GERD symptoms 6
• Combine with antireflux dietary modifications 6

Refractory Cases

If cough persists after 4 weeks of inhaled corticosteroids:

• Verify proper inhaler technique and medication compliance before escalating therapy 2
• Repeat induced sputum analysis to assess persistent airway eosinophilia 2
• If persistent eosinophilia (≥3%) is documented, escalate to oral prednisone 40 mg daily for 1-2 weeks, followed by continuation of inhaled corticosteroids 2, 8
• Consider adding leukotriene receptor antagonist before systemic corticosteroids if compliance is confirmed 2

Treatment for Coexisting UACS

• First-generation antihistamine/decongestant combination (brompheniramine with sustained-release pseudoephedrine) for postnasal drainage symptoms 2
• Nasal topical corticosteroids if allergic rhinitis component is present 9

Critical Pitfalls to Avoid

• Do not diagnose asthma based solely on cough without documenting airway hyperresponsiveness or reversible airflow obstruction—this leads to inappropriate long-term bronchodilator therapy 2, 1
• Do not assume all eosinophilia with cough is pulmonary—failure to exclude hematologic malignancy in patients with absolute eosinophil count >1.5 × 10⁹/L can delay diagnosis of life-threatening conditions like chronic eosinophilic leukemia 4
• Do not stop inhaled corticosteroids prematurely—80% of patients with NAEB require long-term maintenance therapy for cough suppression 2
• Do not overlook occupational or environmental allergen exposures that may be driving the eosinophilic inflammation 2