What is the best course of treatment for a patient with a persistent dry cough for a year, worsened at night, with nasal congestion, elevated absolute eosinophils, and multiple nodules on CT scan, who experiences relief with albuterol (albuterol) but not with loratadine (loratadine) or nasal spray?

Management of Persistent Eosinophilic Cough with Pulmonary Nodules

This patient requires immediate investigation of the pulmonary nodules with bronchoscopy or biopsy to exclude malignancy or parasitic infection, followed by inhaled corticosteroid therapy (budesonide 400 μg twice daily) for presumed non-asthmatic eosinophilic bronchitis (NAEB). 1, 2

Critical First Step: Evaluate the Pulmonary Nodules

The presence of multiple nodules on CT scan with elevated eosinophils (697 cells/μL, which is above normal range of <500) demands urgent investigation before initiating empiric therapy. 1

Key diagnostic considerations:

• Parasitic infection (toxocariasis): Multiple bilateral lung nodules with ground glass halo pattern combined with peripheral eosinophilia is characteristic of pulmonary toxocariasis, which requires specific serologic testing and Western blot confirmation 3

• Malignancy: CT findings of nodules require direct investigation via bronchoscopy with transbronchoscopic biopsy or CT-guided fine-needle aspiration to exclude endobronchial tumor or other malignancies 1

• Eosinophilic lung disease: The combination of nodules, eosinophilia, and cough responsive to albuterol suggests either NAEB or eosinophilic pneumonia, which have different treatment approaches 2

Critical pitfall: Do not use inhaled corticosteroids for eosinophilic pneumonitis, as treatment failure occurs in 100% of cases—this is a distinct condition from NAEB 2

Diagnostic Workup Algorithm

Immediate investigations needed:

1. Bronchoscopy with bronchoalveolar lavage (BAL) to assess for eosinophilic alveolitis and obtain tissue diagnosis of nodules 3, 1

2. Induced sputum for eosinophil count to confirm NAEB diagnosis (if properly performed sputum induction is available) 1

3. Parasitic serologies including toxocariasis testing given the nodular pattern and eosinophilia 3

4. Occupational and environmental history to identify potential allergen or sensitizer exposure 2, 1

Treatment Strategy After Nodule Evaluation

If Nodules Are Benign and NAEB Is Confirmed:

First-line therapy: Inhaled corticosteroids 2, 1

• Budesonide 400 μg inhaled twice daily is the evidence-based regimen that demonstrates significant improvement in cough symptoms and reduction in sputum eosinophils within 4 weeks 2

• This regimen normalizes capsaicin cough sensitivity after 4 weeks of treatment 2

• The diagnosis of NAEB is confirmed by demonstrating both airway eosinophilia AND improvement in cough following corticosteroid therapy 1, 2

Why this patient likely has NAEB:

• Normal pulmonary function tests and 6-minute walk test exclude significant airflow obstruction 1
• Cough relief with albuterol suggests bronchial hyperreactivity without asthma 1
• Nocturnal cough worsening is consistent with eosinophilic airway inflammation 1
• Elevated absolute eosinophils support eosinophilic bronchitis 2

Addressing the Upper Airway Component:

The nasal congestion unresponsive to loratadine or nasal spray suggests this is NOT the primary driver of cough, but requires optimization: 1

• Switch from loratadine to intranasal corticosteroid (fluticasone, mometasone, or budesonide) as first-line therapy for persistent nasal symptoms 4

• Loratadine (a second-generation antihistamine) is ineffective for nonallergic rhinitis and provides limited benefit for nasal congestion even in allergic rhinitis 4, 5

• First-generation antihistamine-decongestant combination (such as brompheniramine with sustained-release pseudoephedrine) should be tried if intranasal corticosteroid fails, as this is the recommended empiric treatment for upper airway cough syndrome (UACS) 1

Important caveat: Chronic cough is frequently multifactorial, and both UACS and NAEB may coexist. The cough will not resolve until both conditions are effectively treated. 1

Escalation for Refractory Cases

If symptoms persist despite high-dose inhaled corticosteroids: 2, 1

• Add oral corticosteroids (prednisone 1-2 week course) for patients with persistently troublesome symptoms or when eosinophilic inflammation progresses despite maximal inhaled therapy 2, 1

• Consider leukotriene receptor antagonist (montelukast) as an adjunct before escalating to systemic corticosteroids 1

Monitoring Response

Expected timeline and markers: 2

• Clinical improvement in cough should occur within 4 weeks of initiating inhaled corticosteroids 2
• Monitor sputum eosinophil counts (if available) to assess treatment response 2
• The reduction in cough sensitivity correlates positively with reduction in sputum eosinophil count 2

If no improvement after 4 weeks of inhaled corticosteroids:

• Reassess for alternative diagnoses including gastroesophageal reflux disease (GERD), which commonly coexists with other causes of chronic cough 1
• Consider referral to a cough specialist 1

Key Clinical Pitfalls to Avoid

1. Do not assume NAEB without confirming airway eosinophilia via induced sputum or BAL—patients with chronic cough without sputum eosinophilia do not respond to inhaled corticosteroids 2

2. Do not delay investigation of pulmonary nodules with empiric therapy—malignancy and parasitic infections require specific treatment 1, 3

3. Do not continue ineffective therapies—loratadine has already failed and should be discontinued in favor of intranasal corticosteroids or first-generation antihistamine-decongestant combinations 1, 4

4. Do not treat as asthma alone—normal spirometry and lack of variable airflow obstruction make classic asthma unlikely, though bronchial hyperreactivity may be present 1