What is the best management approach for a patient with chronic cough and fever with negative sputum culture and CBNAAT results?

Management of Chronic Cough and Fever with Negative Sputum Culture and CBNAAT

For patients with chronic cough and fever with negative sputum culture and CBNAAT results, a systematic evaluation targeting the most common causes of chronic cough (upper airway cough syndrome, asthma, non-asthmatic eosinophilic bronchitis, and GERD) should be initiated, with empiric sequential treatment while ruling out serious underlying conditions. 1

Initial Evaluation

1. Rule out serious conditions first:

   • Check for red flags: hemoptysis, significant weight loss, persistent fever, focal chest findings 2
   • Obtain chest radiograph (essential) 1, 2
   • Consider high-resolution CT scan if chest radiograph is normal but suspicion remains high 1

2. Consider common causes of chronic cough with fever:

   • Post-infectious cough (subacute, 3-8 weeks)
   • Tuberculosis (despite negative CBNAAT - culture-negative TB)
   • Non-tuberculous mycobacterial infection
   • Bronchiectasis
   • Chronic bronchitis
   • Non-asthmatic eosinophilic bronchitis (NAEB)

Management Algorithm

Step 1: Evaluate for Culture-Negative Tuberculosis

Despite negative sputum culture and CBNAAT, tuberculosis should still be considered in appropriate clinical and epidemiological settings 1.

• If clinical suspicion for TB remains high:
  • Consider bronchoscopy with bronchoalveolar lavage and biopsy 1
  • If radiographic findings are consistent with active TB, empiric anti-TB therapy with INH, RIF, PZA, and EMB is warranted 1
  • Evaluate clinical and radiographic response after 2 months of therapy 1

Step 2: Sequential Empiric Treatment for Common Causes

1. Upper Airway Cough Syndrome (UACS):

   • First-generation antihistamine/decongestant combination for 2-4 weeks 2
   • Consider intranasal corticosteroids if prominent nasal symptoms 2

2. Asthma/Bronchial Hyperresponsiveness:

   • If UACS treatment fails, consider asthma
   • Ideally perform bronchoprovocation challenge (BPC) if spirometry is normal 1
   • Trial of inhaled corticosteroids and bronchodilators for 4 weeks 2
   • Consider short course of oral corticosteroids if high suspicion 1

3. Non-Asthmatic Eosinophilic Bronchitis (NAEB):

   • If asthma treatment fails, consider NAEB
   • Ideally perform induced sputum test for eosinophils 1
   • If testing unavailable, empiric trial of inhaled corticosteroids 1
   • For persistent symptoms despite high-dose ICS, oral corticosteroids should be given 1

4. Gastroesophageal Reflux Disease (GERD):

   • If above treatments fail, consider GERD
   • Proton pump inhibitor with lifestyle modifications for 4-8 weeks 2

Step 3: Evaluate for Less Common Causes

If the above approach fails:

1. Bronchiectasis:

   • High-resolution CT scan is diagnostic procedure of choice 1
   • Consider bronchodilators if airflow obstruction is present 1

2. Chronic Bronchitis:

   • For acute exacerbations, short course (10-15 days) of systemic corticosteroids is effective 1
   • Central cough suppressants (codeine, dextromethorphan) recommended for short-term symptomatic relief 1
   • Avoid long-term oral corticosteroids for chronic bronchitis 1

Important Considerations

• Multiple causes: Chronic cough often has multiple simultaneous causes requiring sequential and additive therapy 1, 3
• Avoid unnecessary antibiotics: Unless clear evidence of bacterial infection exists, routine antibiotic treatment is not justified 2
• Smoking cessation: Essential for patients who smoke 1
• ACE inhibitors: Should be discontinued if patient is taking them 1
• Refractory cough: Consider neuromodulators (gabapentin) or speech therapy for cough suppression techniques if all else fails 2, 4

When to Refer

If cough persists despite thorough evaluation and appropriate treatment trials, referral to a pulmonologist or cough specialist is indicated 1, 4.