What is the approach to a patient with a chronic cough, sputum production, and shortness of breath (SOB) on exertion, with a baseline eosinophil count of 54%?

Approach to Chronic Cough with Sputum, Dyspnea on Exertion, and 54% Eosinophilia in a CLD Patient

This patient with 54% eosinophils requires immediate sputum analysis to confirm eosinophilic airway inflammation and a trial of inhaled corticosteroids, as this markedly elevated eosinophil count strongly suggests either nonasthmatic eosinophilic bronchitis (NAEB) or eosinophilic asthma, both of which are highly corticosteroid-responsive conditions. 1

Immediate Diagnostic Priorities

Confirm Eosinophilic Airway Inflammation

• Obtain induced sputum analysis to document sputum eosinophilia (>3% non-squamous cell eosinophil count is diagnostic; this patient's 54% is dramatically elevated) 1
• A peripheral blood eosinophil count of 54% is extraordinarily high and suggests significant eosinophilic inflammation requiring urgent evaluation 1
• Perform spirometry with bronchodilator testing to assess for variable airflow obstruction and determine if this represents asthma versus NAEB 1

Distinguish Between Key Diagnoses

If spirometry shows normal airflow and no bronchodilator response:

• Perform methacholine challenge testing (PC20 >16 mg/mL excludes asthma) 1
• Normal spirometry + normal airway hyperresponsiveness + sputum eosinophilia = Nonasthmatic Eosinophilic Bronchitis 1
• NAEB accounts for 10-30% of chronic cough cases in specialist settings and responds excellently to inhaled corticosteroids 1

If spirometry shows airflow obstruction or positive bronchodilator response:

• This suggests cough-variant asthma or classic asthma with eosinophilic inflammation 1, 2
• Proceed with asthma management protocol using inhaled corticosteroids 1

If spirometry shows fixed airflow obstruction in a baseline CLD patient:

• Consider COPD with eosinophilic phenotype (mixed inflammatory pattern) 1
• Sputum eosinophilia >3% in COPD patients predicts corticosteroid responsiveness 1

Immediate Therapeutic Intervention

Initiate Corticosteroid Trial

Start inhaled corticosteroids immediately while diagnostic workup proceeds, given the extremely high eosinophil count 1:

• Budesonide 400 mcg twice daily or equivalent inhaled corticosteroid 3
• The dose-response curve for inhaled corticosteroids plateaus at low doses (≤200 mcg/day beclomethasone equivalent) in most patients 1
• Expect clinical response within 6 hours to 2 weeks 1
• If no response to inhaled corticosteroids after 2 weeks, escalate to oral prednisolone 30 mg/day for 2 weeks 1

Monitor Treatment Response

• Repeat sputum eosinophil count after 2-4 weeks to document reduction (expect 50-70% decrease) 1, 3
• A halving of sputum eosinophil count is clinically significant and indicates treatment response 1
• Assess cough severity subjectively and objectively 4

Additional Diagnostic Considerations

Measure Fractional Exhaled Nitric Oxide (FeNO)

• FeNO >50 ppb (>35 ppb in children) strongly suggests eosinophilic airway inflammation and corticosteroid responsiveness 1
• FeNO provides non-invasive confirmation of eosinophilic inflammation when sputum analysis is unavailable 1
• High FeNO predicts excellent response to inhaled corticosteroids 1

Exclude Alternative Diagnoses

Rule out upper airway cough syndrome (UACS):

• Examine for rhinorrhea, postnasal drip, sinus tenderness 1
• Consider sinus imaging if clinical features suggest chronic sinusitis 1
• UACS can coexist with eosinophilic bronchitis in up to 30% of cases 1

Rule out gastroesophageal reflux disease (GERD):

• GERD is a common comorbidity but typically does not cause 54% eosinophilia 1
• Consider empiric proton pump inhibitor trial if GERD symptoms present 1

Rule out occupational exposures:

• Detailed occupational history for organic dusts, cotton, hemp, or other industrial exposures 5
• Occupational eosinophilic bronchitis can present identically to idiopathic NAEB 5

Rule out parasitic infection or drug reaction:

• 54% peripheral eosinophilia is unusually high even for NAEB and warrants consideration of systemic causes 6
• Review medication list for potential drug-induced eosinophilia 6

Prognosis and Long-Term Management

Natural History

• NAEB can be transient, episodic, or persistent 1, 7
• Some patients require long-term maintenance inhaled corticosteroids 1, 4
• Approximately 30% of patients with isolated cough and eosinophilia may develop typical asthma symptoms over several years 2
• Some NAEB patients may develop fixed airflow obstruction resembling COPD 7

Monitoring Strategy

• Sputum-guided therapy reduces exacerbations by up to 60% in patients with eosinophilic inflammation 1
• Monitor sputum eosinophil counts every 3-6 months to guide corticosteroid dosing 1, 4
• Persistent sputum eosinophilia despite treatment predicts future exacerbations 1

Critical Pitfalls to Avoid

Do not assume this is simple COPD exacerbation in a baseline CLD patient—the 54% eosinophilia demands specific evaluation for eosinophilic bronchitis or asthma 1

Do not withhold corticosteroids pending complete diagnostic workup—the extremely high eosinophil count justifies immediate empiric treatment 1

Do not diagnose asthma without objective testing—many patients with eosinophilic bronchitis are misdiagnosed as asthmatic and receive inappropriate long-acting beta-agonists 1

Do not stop corticosteroids abruptly after initial response—taper slowly and monitor for recurrence of eosinophilia 4, 3