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

Management of Persistent Cough

All patients with persistent cough should receive a chest radiograph and spirometry as baseline investigations, followed by sequential empiric treatment targeting the three most common causes: upper airway cough syndrome (UACS), asthma, and gastroesophageal reflux disease (GERD). 1, 2

Initial Assessment and Risk Stratification

Immediate Actions

• Obtain a chest radiograph in all patients with chronic cough to exclude pneumonia, malignancy, structural abnormalities, interstitial disease, or congestive heart failure 1, 2
• Perform spirometry with bronchodilator response testing in all patients with chronic cough to identify airflow obstruction 1
• Stop ACE inhibitor immediately if the patient is taking one, as cough typically resolves within days to 2 weeks (median 26 days) after discontinuation 2
• Counsel smoking cessation, as chronic bronchitis from smoking can resolve within 4 weeks in most patients 2

Red Flags Requiring Expanded Workup

• Fever, night sweats, weight loss, or history of tuberculosis, cancer, or AIDS warrant immediate expanded differential diagnosis 2
• Finger clubbing in a smoker with pleural effusion or lobar collapse strongly suggests bronchogenic carcinoma 1

Sequential Empiric Treatment Algorithm

Step 1: Treat Upper Airway Cough Syndrome (UACS) First

• Initiate a first-generation antihistamine-decongestant combination for 1-2 weeks as first-line therapy 1, 2
• Clinical pointers for UACS include nasal discharge, throat clearing, postnasal drip sensation, nasal congestion, or rhinorrhea 2
• This is the most appropriate initial empiric treatment even without definitive diagnostic testing 1

Step 2: Evaluate and Treat Asthma if UACS Treatment Fails

• Suspect asthma when cough worsens at night, with cold air exposure, or with exercise 2
• Spirometry may be normal in cough-variant asthma, as many patients do not exhibit airflow obstruction 1
• Bronchoprovocation challenge testing is the preferred diagnostic test when spirometry is normal or near-normal (FEV1 >70% predicted) 1, 2
• Peak expiratory flow (PEF) measurements should be avoided as they are less accurate than FEV1 for diagnosing airflow obstruction 1
• Initiate combination therapy with inhaled corticosteroids, inhaled β-agonists, or oral leukotriene inhibitors 1
• Response to bronchodilators may occur within 1 week, but complete resolution can take up to 8 weeks 2
• For patients with normal spirometry and bronchodilator response, offer a therapeutic trial of prednisolone to evaluate for cough-predominant asthma or eosinophilic bronchitis 1

Step 3: Treat GERD if Both UACS and Asthma Treatments Fail

• Initiate intensive GERD therapy including high-dose PPI, dietary modifications, and lifestyle changes 1, 2
• GERD therapy requires patience, as response may take 2 weeks to several months, with some patients requiring 8-12 weeks before improvement 2
• Add a prokinetic agent such as metoclopramide and rigorous adherence to dietary measures before labeling the patient as having medically refractory GERD 1
• Consider that cough may persist due to non-acid reflux disease after elimination of gastric acid and may respond to surgical fundoplication 1

Advanced Diagnostic Testing for Refractory Cases

Proceed to advanced testing only after adequate therapeutic trials of UACS, asthma, and GERD have failed 2

Secondary Care Investigations

• Bronchoscopy should be undertaken in all patients in whom inhalation of a foreign body is suspected 1
• Bronchoscopy may be useful in patients in whom other targeted investigations are normal, though diagnostic yield is low (1-6%) 1
• High-resolution CT (HRCT) scanning may be useful in patients with persistent atypical cough when other investigations are normal 1, 2
• HRCT is more sensitive than plain chest radiography for diagnosing bronchiectasis and diffuse pulmonary diseases, showing abnormalities in up to 42% of patients with normal chest radiographs 1
• Order 24-hour esophageal pH monitoring if empiric GERD therapy failed 2

Important Nuances About Diagnostic Testing

Studies from general respiratory clinics have reported poor diagnostic and treatment outcomes compared with specialist cough clinics that use comprehensive management algorithms 1. Extrapulmonary causes, particularly gastroesophageal reflux, are frequently overlooked 1. The presence of non-asthmatic corticosteroid-responsive cough syndromes (eosinophilic bronchitis) emphasizes the importance of assessing airway inflammation or offering a trial of corticosteroids in all patients with chronic cough, irrespective of test results for variable airflow obstruction and airway hyperresponsiveness 1.

Management of Truly Refractory Chronic Cough

Only diagnose unexplained cough after completing systematic evaluation and adequate therapeutic trials of all common causes 1, 2

Treatment Options for Refractory Cough

• Consider gabapentin trial starting at 300mg once daily, escalating as tolerated to maximum 1,800mg daily in divided doses 2
• Multimodality speech pathology therapy is a reasonable alternative approach 2
• Low-dose morphine may be considered but carries addiction risk 2
• Before making the diagnosis of unexplained cough, consider referral to a cough specialist 1

Special Consideration: Post-Infectious Cough (Subacute Cough)

If cough began with an acute respiratory infection 3-8 weeks ago, consider post-infectious cough 2, 3

• Inhaled ipratropium bromide is first-line therapy for post-infectious cough 2, 3
• Inhaled corticosteroids if ipratropium fails 2
• Short course of oral prednisone for severe paroxysms after ruling out other causes 2
• Reassurance that spontaneous resolution is expected within 3-8 weeks total from symptom onset 3

Critical Pitfalls to Avoid

• Do not rely on single PEF measurements for diagnosing airflow obstruction, as they are less accurate than FEV1 1
• Do not assume normal spirometry excludes asthma as a cause of chronic cough, since cough-variant asthma and eosinophilic bronchitis may not exhibit airflow obstruction or bronchial hyperresponsiveness 1
• Do not proceed with extensive diagnostic testing before completing adequate therapeutic trials of the three most common causes (UACS, asthma, GERD) 2
• Do not forget that more than one cause may be present simultaneously, requiring sequential and additive therapy 1
• Do not overlook ACE inhibitor use as a reversible cause of chronic cough 2
• Recognize the 8-week threshold where post-infectious cough becomes chronic cough requiring different evaluation 3