Differentials

COPD

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

History of smoking.

Dyspnoea occurs with or without wheezing and coughing.

Examination may show barrel chest, hyper-resonance to percussion, and distant breath sounds.

INVESTIGATIONS

Post-bronchodilator spirometry showing an obstructive pattern with FEV₁/FVC ratio <70% or lower limit of normal (LLN).

CXR showing hyper-inflation of the lungs.

Chronic rhinosinusitis

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SIGNS / SYMPTOMS

May present with nocturnal cough and dyspnoea from post-nasal discharge.

May co-exist with asthma.

INVESTIGATIONS

Anterior rhinoscopy or nasal endoscopy may show inflammation, purulent discharge, oedema, or frank polyps.

CT may show opacification of involved sinuses, mucosal thickening, air-fluid levels, or anatomical abnormalities.

Breathing pattern disorder

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Breathing pattern disorder (BPD) is a common cause of unexplained dyspnoea in athletes with variable symptoms and normal investigations.[80][81]

​Breathlessness, light-headedness, and peripheral tingling are common. In athletes, there should be a low threshold for ruling out BPD.[81]

BPD may be comorbid with exercise-induced laryngeal obstruction and exercise-induced bronchoconstriction. Hyperventilation syndrome is the most common BPD, but other forms may co-exist or appear in isolation.

INVESTIGATIONS

Diagnosis of exclusion. Screening for hyperventilation with Nijmegen questionnaire (score >23 suggestive of hyperventilation). Cardiopulmonary exercise testing may help differentiate BPD.[81]

Exercise-induced laryngeal obstruction

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Symptoms associated with exercise-induced laryngeal obstruction (EILO) typically include noisy breathing and upper chest/throat discomfort or restriction, and are amplified during intense exercise.[81]

In athletes, there should be a low threshold for ruling out EILO.[81]

INVESTIGATIONS

Continuous laryngoscopy during exercise is the gold-standard test for assessing exercise-related laryngeal conditions.[81]

Vocal cord dysfunction

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Throat tightness, hoarse voice or voice changes, cough and throat clearing.

May be a differential or may co-exist with asthma and poorly-controlled symptoms.

INVESTIGATIONS

Direct visualisation of the vocal cords with rhinolaryngoscopy during a spell. Inspiratory flow volume loop is helpful when abnormal (flattened).

Bronchiectasis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Increased sputum production, dyspnoea, cough, and wheezing and, if severe, recurrent pulmonary infections.

INVESTIGATIONS

High-resolution CT chest: dilated airways, bronchial wall thickening.

Can occasionally be seen on CXR.

Congestive heart failure

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

History of coronary artery disease or uncontrolled hypertension.

Examination shows dependent oedema, elevated jugular venous pressure, and basal pulmonary crepitations.

INVESTIGATIONS

ECG usually abnormal. CXR may show increased alveolar markings, fluid in fissures, and pleural effusions.

Echocardiogram may show reduced or preserved left ventricular ejection fraction. Natriuretic peptides may be elevated.

Cystic fibrosis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Chronic, sometimes productive cough with a possible family history of cystic fibrosis.

Nasal polyposis at or before 12 years of age and symptoms related to other organ involvement, such as diarrhoea, malabsorption, or failure to thrive.

INVESTIGATIONS

Sweat chloride testing: level of sweat chloride ≥60 mmol/L (≥60 mEq/L).

Consider repeat testing.

Tracheomalacia

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Symptoms are usually positionally dependent.

Expiratory stridor and a barking brassy cough, wheezing, and possibly additional breath sound at the end of expiration (the bagpipe sign) are common. Less common findings are inspiratory stridor, episodes of holding of breath, anoxia, recurrent respiratory infections, retraction of intercostal and subcostal muscles, failure to thrive, and respiratory and cardiac arrest.[82]

INVESTIGATIONS

Dynamic CT using volumetric analysis may be helpful in the initial diagnosis of tracheomalacia, with reported accuracy rates as high as 97%.[83] Confirmatory testing with bronchoscopy may be performed as indicated, which remains the gold standard for diagnosis. For diagnosis, bronchoscopy must demonstrate ≥50% decrease in airway lumen size on forced expiration.

Vascular ring

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Wheezing, shortness of breath, occasional stridor.

INVESTIGATIONS

CT chest with contrast: double aortic arch, abnormal take-off of the innominate artery, anomaly of left pulmonary artery, right aortic arch, aberrant right subclavian, enlarged pulmonary veins.[82]

Foreign body aspiration

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Wheezing, shortness of breath, occasional stridor are common.

If the foreign body is in the peripheral airway, localised one-sided wheezing or collapse of the distal lung tissue is found.

INVESTIGATIONS

CXR, CT chest, or bronchoscopy shows the foreign body.

Recurrent retrograde aspiration

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Gastro-oesophageal reflux disease (GORD) may lead to aspiration. GORD is a clinical diagnosis that presents with heartburn and regurgitation. Prevalent in patients with poorly controlled asthma.[49]

The link between GORD and the development of asthma remains unclear, but could be related to chronic irritation and inflammation of the airways following exposure to gastric contents.[50][51]

Treating symptomatic GORD can moderately improve lung function and use of rescue medication in patients with moderate-to-severe asthma.[52]

INVESTIGATIONS

Symptomatic improvement after treating GORD; focal signs of pneumonitis or pneumonia on chest radiography.

Alpha-1 antitrypsin deficiency

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Breathlessness, wheeze.

May have family history of lung disease.

Often early diagnosis of COPD (e.g., under 40 years) or severity of radiographic disease out of proportion to smoking history.

INVESTIGATIONS

Testing for the alpha-1 antitrypsin phenotype.

Pulmonary embolism

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

A wide variety of presentations. Symptoms typically have an acute onset. Common clinical features include dyspnoea, pleuritic chest pain, and hypoxaemia.[84]

INVESTIGATIONS

Risk stratification with appropriate scoring systems and serum D-dimer measurements should be done.

CT pulmonary angiography (CTPA) is the preferred investigation for definitive confirmation of pulmonary embolism. The less sensitive ventilation-perfusion (V/Q) scan can be used as an alternative to CTPA.[84]

Common variable immunodeficiency

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

History of recurrent, usually sinopulmonary, infections.

INVESTIGATIONS

Serum IgG level <5g/L (500 mg/dL). Generally presents with bronchiectasis on imaging.

Pertussis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

History and examination reveal prolonged paroxysms of barking cough, sometimes with stridor.

These symptoms usually warrant further investigation.

INVESTIGATIONS

Diagnosis can usually be confirmed by culture of a nasopharyngeal aspirate or swab from the posterior nasopharynx (e.g., with or without nucleic acid amplification testing).

Serology and full blood count testing can be useful.

Important to diagnose and treat early.

Tuberculosis

SIGNS / SYMPTOMS
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SIGNS / SYMPTOMS

Chronic cough, haemoptysis, dyspnoea.

Fatigue, fever, (night) sweats, anorexia, weight loss.

These symptoms warrant further investigation.

INVESTIGATIONS

CXR is almost always abnormal, typically showing fibronodular opacities in upper lobes, with or without cavitation.

Other tests include sputum acid-fast bacilli smear, sputum culture, full blood count, and nucleic acid amplification tests (on at least one respiratory specimen).

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