What is the appropriate management for a patient with a persistent cough?

Management of Persistent Cough

All patients with persistent cough (>8 weeks) require chest radiograph and spirometry as mandatory baseline investigations, followed by systematic evaluation and treatment of the most common causes: upper airway cough syndrome (UACS), asthma, gastroesophageal reflux disease (GERD), and nonasthmatic eosinophilic bronchitis (NAEB). 1

Initial Assessment and Red Flags

Immediately assess for life-threatening conditions before proceeding with chronic cough evaluation:

• Hemoptysis, fever, night sweats, weight loss, or history of tuberculosis, cancer, or AIDS require urgent expanded workup 2
• In smokers, examine specifically for finger clubbing combined with pleural effusion or lobar collapse—this strongly suggests bronchogenic carcinoma 1, 2
• Cough is the fourth most common presenting feature of lung cancer 2
• Discontinue ACE inhibitors immediately in all patients with troublesome cough—no patient should continue these medications 1

Mandatory Baseline Investigations

Chest radiograph is required in all patients with chronic cough:

• Approximately 31% of chest radiographs will be abnormal or yield a diagnosis 1, 2
• If abnormal findings account for symptoms, investigate appropriately rather than using chronic cough algorithms 1

Spirometry with bronchodilator response testing is mandatory:

• Measure FEV1 before and after short-acting β2-agonist (salbutamol 400 mcg by MDI with spacer or 2.5 mg by nebulizer) 1
• Critical pitfall: Normal spirometry does NOT exclude asthma or eosinophilic bronchitis as causes 1, 2
• Do NOT use single peak flow measurements—they are less accurate than FEV1 for identifying airflow obstruction 1, 2

Sequential Treatment Algorithm

Step 1: Upper Airway Cough Syndrome (UACS)

Treat first for UACS (formerly postnasal drip syndrome), as this is one of the three most common causes:

• In the presence of prominent upper airway symptoms, prescribe topical intranasal corticosteroid (fluticasone or mometasone) 1, 3
• Add first-generation antihistamine/decongestant combination (brompheniramine/pseudoephedrine or chlorpheniramine/phenylephrine) 3
• Start once-daily at bedtime for 2-3 days, then advance to twice-daily to minimize sedation 3
• Critical warning: Do NOT use nasal decongestant sprays for more than 3-5 days due to rebound congestion risk 3

Step 2: Asthma/NAEB Evaluation

If UACS treatment fails after 2 weeks, proceed to asthma evaluation:

• Bronchial provocation testing should be performed in patients without clinically obvious etiology who have normal spirometry 1
• If bronchial provocation testing is unavailable and baseline spirometry is normal, initiate empiric asthma treatment 1

For confirmed or suspected asthma:

• Begin with inhaled β2-agonists and inhaled corticosteroids 1
• If inadequate response, patients with normal spirometry and bronchodilator response should be offered a therapeutic trial of oral prednisolone for 2 weeks 1
• Cough is unlikely to be due to eosinophilic airway inflammation if there is no response to a 2-week oral steroid trial 1
• Consider adding leukotriene inhibitor before oral corticosteroid 1

For NAEB diagnosis:

• Induced sputum test to determine increased eosinophils is the diagnostic test of choice 1
• NAEB should be considered after UACS and asthma because diagnosis is straightforward and response to treatment is very predictable 1

Step 3: Gastroesophageal Reflux Disease (GERD)

If cough persists after adequate trials of UACS and asthma treatment, evaluate for GERD:

• Critical point: Failure to consider GERD as a cause for cough is a common reason for treatment failure 1
• Reflux-associated cough may occur in the absence of gastrointestinal symptoms 1

Empiric GERD treatment is recommended for patients with this clinical profile:

• Cough >2 months, normal chest radiograph, nonsmoker, not on ACE inhibitors, failed UACS and asthma treatment 1
• This profile has 92% probability of GERD-induced cough 1

GERD treatment protocol:

• Intensive acid suppression with high-dose proton pump inhibitors (omeprazole 40 mg twice daily) and alginates should be undertaken for a minimum of 3 months 1, 3
• Add dietary modifications and lifestyle changes 3
• Critical timing issue: GERD-related cough may require 2 weeks to several months for response, with some patients needing 8-12 weeks 3, 2
• If inadequate response, add prokinetic agent (metoclopramide) and rigorous adherence to dietary measures 1

For patients without GERD symptoms:

• Ideally perform 24-hour esophageal pH monitoring, though interpretation criteria vary 1
• Given limited availability and interpretation issues, empiric trial of antireflux therapy is reasonable 1

Step 4: Advanced Evaluation for Refractory Cough

If all empiric treatments fail after adequate trials (minimum 3 months for GERD), proceed with advanced testing:

• High-resolution CT chest to evaluate for bronchiectasis, interstitial lung disease, or occult masses 1, 3, 2
• 24-hour esophageal pH monitoring if GERD remains suspected despite failed empiric therapy 3, 2
• Bronchoscopy should be undertaken in all patients in whom inhalation of a foreign body is suspected 1
• Bronchoscopy may be useful to evaluate for endobronchial tumor, sarcoidosis, suppurative lower airway infection, eosinophilic or lymphocytic bronchitis 1, 3, 2

In countries where tuberculosis is common:

• Obtain expectorated or induced sputum samples with acid-fast staining or bronchoscopy to detect occult endobronchial tuberculosis 1

Special Considerations

Post-Infectious Cough (Subacute Cough)

If cough duration is 2-8 weeks following respiratory infection:

• Prescribe inhaled ipratropium bromide 2-3 puffs four times daily—this has the strongest evidence for attenuating post-infectious cough 3, 2
• Provide reassurance that post-infectious cough typically resolves spontaneously within 3-8 weeks total from symptom onset 2
• Do NOT prescribe antibiotics unless bacterial sinusitis or pertussis is confirmed 2

Pertussis Evaluation

If paroxysmal cough, post-tussive vomiting, or inspiratory whooping sound present:

• Pertussis must be ruled out first, even in vaccinated patients, as breakthrough infections occur 3
• Obtain nasopharyngeal culture for Bordetella pertussis 3, 2
• If pertussis is confirmed or highly suspected, prescribe macrolide antibiotics immediately (azithromycin or clarithromycin) 3
• Pertussis accounts for approximately 10% of chronic cough cases in some series 2

Smoking-Related Cough

Smoking is one of the commonest causes of persistent cough and appears dose-related:

• Smoking cessation should be encouraged as it is accompanied by significant remission in cough symptoms 1

Refractory/Unexplained Chronic Cough

Before diagnosing unexplained cough:

• Chronic cough should only be considered idiopathic following thorough assessment at a specialist cough clinic 1
• Do NOT diagnose "unexplained cough" until completing systematic evaluation of UACS, asthma, and GERD with adequate treatment trials 3
• Referral to a specialist cough clinic should be encouraged 1

For confirmed refractory chronic cough:

• Consider gabapentin trial starting at 300 mg once daily, escalating as tolerated to maximum 1,800 mg daily in divided doses 2
• Multimodality speech pathology therapy is a reasonable alternative 2
• Low-dose morphine may be considered but carries addiction risk 2

Critical Pitfalls to Avoid

• Do NOT continue ACE inhibitors in any patient with troublesome cough 1
• Do NOT use single peak flow measurements for diagnosis 1, 2
• Do NOT abandon GERD therapy prematurely—it may require 8-12 weeks for response 2
• Do NOT inappropriately prescribe antibiotics for non-bacterial post-infectious cough 2
• Do NOT assume GERD is ruled out simply because of prior antireflux surgery, as reflux can persist 3
• Do NOT fail to recognize that more than one cause may be present simultaneously—sequential and additive therapy may be crucial 1

Treatment Monitoring

Treatment effects should be formally quantified using:

• Cough-specific quality of life questionnaires 1
• Cough visual analogue scores as an alternative, though less well validated 1

Optimal management comprises a combination of diagnostic testing and treatment trials based on the most probable causes, with formal quantification of treatment effects. 1