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

Eosinophilia with Chronic Cough and Laryngitis

The most likely diagnosis is nonasthmatic eosinophilic bronchitis (NAEB), which should be confirmed with induced sputum showing ≥3% eosinophils and treated with inhaled corticosteroids (budesonide 400 μg twice daily for 4 weeks). 1

Diagnostic Approach

Initial Evaluation

Obtain chest radiograph and spirometry as first-line investigations to exclude structural lung disease and assess for airflow obstruction. 1 The laryngitis component suggests upper airway involvement that may be part of the eosinophilic inflammatory process or concurrent gastroesophageal reflux disease (GERD). 1

Key Diagnostic Tests

• Spirometry with bronchodilator response: Normal spirometry with no reversibility helps distinguish NAEB from asthma. 1

• Methacholine challenge test: A provocative concentration >16 mg/mL (normal airway responsiveness) excludes asthma and supports NAEB diagnosis. 1

• Induced sputum analysis: This is the gold standard for confirming eosinophilic airway inflammation. The procedure involves inhaling hypertonic saline (3%, 4%, 5%) sequentially for 5 minutes each after bronchodilator premedication. 1 A differential cell count showing ≥3% eosinophils (non-squamous cells) confirms the diagnosis. 1

• Alternative if sputum induction unavailable: Bronchoscopy with bronchoalveolar lavage showing >25% eosinophils can provide similar diagnostic information. 1, 2

• Exhaled nitric oxide: While elevated in NAEB, its diagnostic role has not been formally validated and should not replace sputum analysis. 1

Exclude Secondary Causes of Eosinophilia

Before confirming NAEB, systematically rule out:

• Parasitic infections: Essential exclusion criterion, particularly in endemic areas. 2, 3

• Drug reactions: Review all medications including ACE inhibitors (common cough trigger). 1, 2

• Allergic bronchopulmonary aspergillosis: Check specific IgE and IgG antibodies. 2

• ANCA-associated vasculitis: Obtain ANCA testing if systemic symptoms present. 2

• Chronic eosinophilic pneumonia: If chest imaging shows peripheral infiltrates or ground-glass opacities, consider this diagnosis requiring higher-dose systemic corticosteroids. 2, 4

• Hypereosinophilic syndrome: Requires peripheral eosinophil count >1.5 × 10⁹/L with end-organ involvement and exclusion of secondary causes. 3, 5

Algorithmic Approach to Chronic Cough with Eosinophilia

1. First, evaluate for upper airway cough syndrome (UACS): The laryngitis suggests possible rhinosinus disease contributing to cough. Trial first-generation antihistamine/decongestant for 1-2 weeks. 1

2. Second, assess for asthma: If UACS treatment fails, perform spirometry and methacholine challenge. If positive, treat with inhaled corticosteroids and bronchodilators. 1

3. Third, test for NAEB: If asthma excluded (normal spirometry, negative methacholine challenge), perform induced sputum analysis. 1

4. Fourth, evaluate for GERD: If cough persists despite treating UACS and NAEB, initiate proton pump inhibitor therapy, especially given the laryngitis component. 1

Multiple causes frequently coexist—sequential and additive therapy is crucial. 1 Do not stop investigating after finding one cause if cough persists.

Treatment

For Confirmed NAEB

Inhaled corticosteroids are first-line therapy. 1 Budesonide 400 μg twice daily for 4 weeks has demonstrated efficacy with improvement in cough sensitivity and reduction in sputum eosinophil counts. 1

• Expected response time: Cough should improve within 4 weeks of initiating therapy. 1

• Monitoring: Repeat induced sputum to confirm reduction in eosinophil count. 1

• Duration unclear: No data guide how long to continue treatment after symptom resolution. 1

• Oral corticosteroids: Occasionally required for refractory cases (prednisolone 0.5 mg/kg/day). 1, 4

For Concurrent GERD (Likely Given Laryngitis)

Initiate proton pump inhibitor therapy empirically, as GERD commonly coexists with eosinophilic airway disease and can cause laryngeal inflammation. 1, 6

If No Response to Initial Therapy

Consider referral to a cough specialist if systematic evaluation and treatment of UACS, asthma/NAEB, and GERD fail to resolve symptoms. 1 For truly unexplained chronic cough with negative eosinophil testing, neuromodulators (gabapentin) may be considered, though inhaled corticosteroids should NOT be used in non-eosinophilic chronic cough. 1

Critical Pitfalls to Avoid

• Do not diagnose asthma based on clinical symptoms alone when eosinophilia is present—objective testing with spirometry and methacholine challenge is mandatory to distinguish NAEB from cough-variant asthma. 1

• Do not use single peak flow measurements for diagnosis—they are inaccurate compared to FEV₁. 1

• Do not prescribe inhaled corticosteroids empirically without confirming eosinophilic inflammation if sputum induction is available, as non-eosinophilic chronic cough does not respond. 1

• Do not assume single etiology—up to 62% of chronic cough cases have multiple contributing factors requiring simultaneous treatment. 1

• Do not delay investigation of systemic eosinophilia (>1.5 × 10⁹/L)—this requires hematologic evaluation to exclude clonal disorders. 3, 5