What are the differential diagnoses for a patient with a persistent cough and diffuse wheezing on auscultation?

Differential Diagnoses for Persistent Cough with Diffuse Wheezing

The most likely diagnosis in a patient presenting with persistent cough and diffuse wheezing on auscultation is asthma (including cough-variant asthma), followed by COPD in smokers, eosinophilic bronchitis, and upper airway cough syndrome. 1

Primary Differential Diagnoses

Asthma and Cough-Variant Asthma

• Asthma is the most common cause of persistent cough with wheezing, particularly when accompanied by a prolonged expiratory phase on auscultation 1
• Cough-variant asthma presents with isolated cough that may worsen at night or after exposure to cold or exercise, and patients may not exhibit obvious wheezing despite having bronchial hyperresponsiveness 1, 2
• Approximately 46% of patients presenting with cough of more than 2 weeks' duration in primary care have asthma or COPD 1
• Eosinophilic airway inflammation is characteristic, and these patients typically respond to inhaled corticosteroids 2

Chronic Obstructive Pulmonary Disease (COPD)

• COPD should be strongly considered in smokers with persistent cough and wheezing, usually accompanied by phlegm production and breathlessness 1
• Smokers with persistent cough are at risk of developing COPD, and productive cough in established airflow obstruction predicts lung function decline 1

Eosinophilic Bronchitis (Non-Asthmatic)

• This condition presents with persistent cough and eosinophilic airway inflammation but lacks the bronchial hyperresponsiveness and variable airflow obstruction seen in asthma 1, 2
• Responds well to inhaled corticosteroids 2

Secondary Differential Diagnoses

Upper Airway Cough Syndrome (Post-Nasal Drip)

• Rhinitis and upper airway disease are among the main causes of chronic cough in specialist cough clinics 1
• May present with wheezing if there is associated lower airway involvement 3

Gastroesophageal Reflux Disease (GERD)

• GERD is one of the three most common causes of chronic cough in secondary care and specialist clinics 1
• Often overlooked in general respiratory clinics but frequently identified in specialist cough clinics 1

Bronchiectasis

• Although typically associated with productive cough, "dry" bronchiectasis can cause persistent cough 1
• Coarse crackles are more prominent than wheezes on examination, but wheezing may be present 1
• History of past respiratory insult should be sought 1

Important Diagnoses Not to Miss

Lung Cancer

• Cough is the fourth most common presenting feature of lung cancer, and persistent cough significantly impairs quality of life 1
• Must be considered especially in smokers with persistent symptoms 4
• Chest radiograph is mandatory in all patients with chronic cough to exclude malignancy 1

Pertussis Infection

• Can cause persistent cough lasting weeks to months 1
• In one series, 10% of chronic cough cases had positive nasal swabs for Bordetella 1

Acute Bacterial Pneumonia

• Should be ruled out with chest X-ray, particularly if fever, productive cough, or systemic symptoms are present 4
• Immediate empiric antibiotic therapy is indicated for high-risk community-acquired pneumonia 4

Congestive Heart Failure

• Can present with cough and wheezing (cardiac asthma) 1
• Look for signs of fluid overload on examination and chest radiograph 3

Critical Initial Workup

Mandatory Investigations

• Chest radiograph should be performed in all patients with chronic cough to identify structural abnormalities, infiltrates, masses, or cardiac enlargement 1
• Spirometry should be performed in all patients with chronic cough to identify airflow obstruction and assess bronchodilator response 1
• If spirometry shows obstruction, measure FEV1 before and after short-acting β2 agonist (salbutamol 400 mcg by MDI with spacer or 2.5 mg by nebulizer) 1

Additional Considerations

• Normal spirometry does not exclude asthma as many patients with cough-variant asthma have normal pulmonary function tests 1
• If asthma or eosinophilic bronchitis is suspected despite normal spirometry, consider a therapeutic trial of prednisolone 1
• Peak expiratory flow measurements are not as accurate as FEV1 and should be avoided for diagnosis 1

Common Pitfalls to Avoid

• Do not assume all wheezing is asthma—consider COPD in smokers, heart failure, and bronchiectasis 1, 5
• Do not overlook extrapulmonary causes such as GERD and upper airway disease, which are frequently missed in general respiratory clinics 1
• Do not rely on single PEF measurements for diagnosis, as they are less accurate than spirometry 1
• In patients with persistent symptoms despite treatment, consider CT chest to evaluate for complications or alternative diagnoses 4