Differential Diagnosis of Dyspnoea / Breathlessness

Author: Mr Vik Veer MBBS(Lond) MRCS(Eng) DoHNS(Eng) — December 2007. Updated 2025.

Pulmonary Causes

Sudden Onset (Seconds to Minutes)

Inhaled Foreign Body

Typical features: Sudden-onset choking, coughing, and unilateral wheeze or stridor. Most common in young children (peanuts, small toys) and in adults with impaired swallow reflex (stroke, bulbar palsy, sedation, dental procedures). If complete obstruction — unable to speak, cough, or breathe — requires immediate Heimlich manoeuvre.

Key investigation: Chest X-ray (may show an opaque object; a radio-lucent object may be evidenced by air trapping with unilateral hyperinflation or mediastinal shift on expiratory film). Rigid bronchoscopy for retrieval.

Pulmonary Embolism (PE)

Typical features: Sudden-onset dyspnoea, pleuritic chest pain, tachycardia, haemoptysis (in pulmonary infarction). Risk factors: immobility, recent surgery, malignancy, thrombophilia, OCP, pregnancy. Massive PE — haemodynamic collapse, right heart strain.

Examination findings: Tachycardia, tachypnoea, reduced oxygen saturation, signs of DVT in the leg. In massive PE: hypotension, raised JVP, right ventricular heave, loud P2, tricuspid regurgitation murmur.

Key investigation: Wells score for pre-test probability, D-dimer (to exclude in low-probability cases), CTPA (gold standard). ECG: sinus tachycardia most common; S1Q3T3 (large S wave in I, Q wave and T wave inversion in III); right bundle branch block. ABG: hypoxaemia with hypocapnia (type I respiratory failure).

Initial management: Oxygen, anticoagulation (DOAC — rivaroxaban or apixaban for haemodynamically stable PE; LMWH as bridge if DOAC not appropriate). Massive PE — systemic thrombolysis (alteplase) or surgical embolectomy. Haemodynamically stable PE with right ventricular dysfunction (submassive) — consider thrombolysis on a case-by-case basis.

Pneumothorax

Typical features: Sudden unilateral sharp pleuritic chest pain and dyspnoea. Primary spontaneous pneumothorax typically affects tall, thin young men without underlying lung disease. Secondary pneumothorax complicates existing lung disease (COPD, asthma, cystic fibrosis, Marfan syndrome, catamenial pneumothorax).

Examination findings: Reduced chest expansion ipsilaterally, hyperresonance to percussion, reduced or absent breath sounds on the affected side. Tension pneumothorax additionally shows tracheal deviation away from the lesion, raised JVP, and haemodynamic compromise.

Key investigation: Chest X-ray (visible pleural edge; absent lung markings lateral to it). Do not delay decompression in tension pneumothorax for imaging.

Initial management: Tension pneumothorax — immediate needle decompression (14G cannula, 2nd ICS mid-clavicular line), followed by chest drain. Primary spontaneous pneumothorax >2 cm on X-ray — aspiration or small-bore chest drain. Secondary pneumothorax — chest drain insertion ± hospital admission regardless of size.

Onset in Hours to Days

Asthma

Typical features: Episodic wheeze, cough, and breathlessness, typically worse at night and in the early morning. Associated with atopy (eczema, allergic rhinitis, hayfever). Triggers include cold air, exercise, allergens, NSAIDs (aspirin-exacerbated respiratory disease), and beta-blockers. Spirometry shows reversible obstructive pattern.

Examination findings: Tachypnoea, tachycardia, bilateral expiratory wheeze, prolonged expiratory phase, use of accessory muscles. In life-threatening asthma: silent chest (no wheeze because no air movement), SpO2 <92%, altered consciousness — call for immediate senior and ICU help.

Key investigation: Peak expiratory flow rate (PEFR) compared to patient's personal best; spirometry; reversibility testing with salbutamol; skin prick or RAST testing for allergens; FeNO (fractional exhaled nitric oxide) to assess eosinophilic airway inflammation.

Initial management (acute exacerbation): High-flow oxygen (target SpO2 94–98%), salbutamol nebulisers, ipratropium bromide nebulisers, prednisolone 40 mg oral (or IV hydrocortisone if unable to swallow), IV magnesium sulphate for severe attacks, ICU referral for life-threatening features.

Pneumonia

Typical features: Dyspnoea developing over hours to days, with fever, productive cough (purulent or rust-coloured sputum), pleuritic chest pain, and systemic features (rigors, myalgia). Causative organisms: Streptococcus pneumoniae (most common); atypicals (Mycoplasma, Legionella, Chlamydophila); Staphylococcus aureus (post-influenzal); Pneumocystis jirovecii (in immunocompromised patients).

Examination findings: Fever, tachycardia, tachypnoea, reduced expansion, dullness to percussion, bronchial breathing, coarse crepitations, and increased vocal resonance over the area of consolidation.

Key investigation: Chest X-ray (consolidation — lobar, multilobar, or diffuse); sputum and blood cultures; FBC (neutrophilia); CRP; urea (for CURB-65 scoring); urinary antigen tests for Legionella and pneumococcus; ABG if severe.

CURB-65 scoring: Confusion (new), Urea >7 mmol/L, Respiratory rate >30/min, BP <90 systolic or <60 diastolic, Age ≥65. Score 0–1: low severity, community treatment; Score 2: moderate severity, consider hospital admission; Score 3–5: high severity, hospital treatment, consider ICU.

Acute Pulmonary Oedema (Left Ventricular Failure)

Typical features: Sudden or rapidly progressive severe breathlessness, orthopnoea (unable to lie flat), paroxysmal nocturnal dyspnoea (waking from sleep gasping), pink frothy sputum. The patient is often extremely distressed. Precipitants include MI, arrhythmia, hypertensive crisis, fluid overload, and non-compliance with medication.

Examination findings: Tachypnoea, tachycardia, hypertension or hypotension (in cardiogenic shock), bilateral fine inspiratory crepitations to mid-zones or upper zones, third heart sound, raised JVP, peripheral oedema. Cold, clammy peripheries in cardiogenic shock.

Key investigation: Chest X-ray (ABCDE of pulmonary oedema — Alveolar shadowing, Kerley B lines, Cardiomegaly, Dilated upper lobe vessels, pleural Effusion). BNP or NT-proBNP (markedly elevated). ECG. Echocardiogram for underlying cause.

Initial management: Sit the patient upright, high-flow oxygen, IV furosemide 40–80 mg, IV morphine 2.5–5 mg (cautiously) for anxiolysis and venodilation, GTN infusion if systolic BP >110 mmHg (not if hypotensive). CPAP/BiPAP non-invasive ventilation for respiratory failure. If cardiogenic shock — inotropes and intra-aortic balloon pump.

Extrinsic Allergic Alveolitis (Hypersensitivity Pneumonitis)

An immune-mediated inflammatory lung disease caused by inhaling organic antigens — classically, farmer's lung (Micropolyspora faeni from mouldy hay) and bird fancier's lung (avian proteins from feathers and droppings). The acute form presents with dyspnoea, fever, and malaise 4–8 hours after allergen exposure. The chronic form leads to pulmonary fibrosis. Ground-glass shadowing on HRCT. Management: allergen avoidance; systemic corticosteroids for acute attacks.

Onset in Days to Weeks

Pleural Effusion

Typical features: Insidious onset of dyspnoea, sometimes with pleuritic pain in early stages. Causes are divided by protein content into transudates (protein <30 g/L) and exudates (protein >30 g/L), using Light's criteria.

Causes — Transudates: Left ventricular failure, hypoalbuminaemia (nephrotic syndrome, liver cirrhosis, malnutrition), hypothyroidism, Meigs syndrome.

Causes — Exudates: Pneumonia (parapneumonic effusion or empyema), malignancy (lung, breast, lymphoma, mesothelioma), pulmonary embolism, TB, pancreatitis, subphrenic abscess, autoimmune disease (SLE, rheumatoid arthritis).

Examination findings: Reduced expansion, stony dullness to percussion, reduced or absent breath sounds, and reduced vocal resonance over the effusion. A friction rub may be heard at the upper border of the effusion.

Key investigation: Chest X-ray (blunting of the costophrenic angle is visible from approximately 300–500 ml; a meniscus sign develops with larger effusions). Thoracic ultrasound for guided aspiration. Pleural fluid analysis: protein, LDH, pH, glucose, amylase, cytology, and culture.

Carcinoma of the Bronchus or Trachea

Lung cancer may cause dyspnoea through direct bronchial obstruction (with collapse or post-obstructive pneumonia), pleural effusion, pericardial effusion, superior vena cava obstruction, lymphangitis carcinomatosa, or phrenic nerve palsy. Associated features: haemoptysis, weight loss, clubbing, Horner's syndrome (Pancoast tumour), and hoarse voice (recurrent laryngeal nerve involvement).

Onset Over Months

Chronic Obstructive Pulmonary Disease (COPD)

Typical features: Progressive dyspnoea on exertion, productive cough, and wheeze in a patient with a significant smoking history. COPD is defined by post-bronchodilator FEV1/FVC ratio <0.7 on spirometry. It is characterised by non-fully reversible airflow obstruction. COPD exacerbations are triggered by respiratory infections (most commonly bacterial — Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis — or viral).

Examination findings: Barrel chest (hyperinflated), pursed-lip breathing, use of accessory muscles, quiet breath sounds, prolonged expiratory phase, wheeze, and in advanced disease: peripheral cyanosis, CO2 retention (bounding pulse, flapping tremor — asterixis), and cor pulmonale (raised JVP, RV heave, peripheral oedema).

Key investigation: Spirometry (obstructive, post-bronchodilator non-reversible); chest X-ray (hyperinflation, flattened diaphragm, bullae); ABG (type II respiratory failure — hypoxaemia with hypercapnia in advanced COPD or acute exacerbation); CT chest for assessment of emphysema distribution and to exclude lung cancer.

Initial management of acute exacerbation: Controlled oxygen (target SpO2 88–92% in known CO2 retainers); salbutamol and ipratropium nebulisers (driven by air not oxygen); prednisolone 30–40 mg oral; antibiotics if purulent sputum or signs of infection; consider NIV (non-invasive ventilation) for type II respiratory failure with pH <7.35.

Pulmonary Fibrosis (Interstitial Lung Disease)

Typical features: Progressive dyspnoea on exertion over months to years, dry non-productive cough, fine inspiratory crackles ("Velcro" crackles) at the lung bases. Clubbing in idiopathic pulmonary fibrosis (IPF). Causes include: idiopathic (IPF), connective tissue disease (RA, scleroderma, SLE, dermatomyositis), occupational (asbestosis — basal fibrosis; silicosis — upper lobe fibrosis), hypersensitivity pneumonitis, drug-induced (methotrexate, nitrofurantoin, amiodarone).

Key investigation: HRCT (honeycombing and traction bronchiectasis in UIP pattern — usual interstitial pneumonia); pulmonary function tests (restrictive pattern — reduced TLC, FVC, DLCO); bronchoscopy with BAL; surgical lung biopsy if diagnosis unclear.

Cardiovascular Causes

MI, Left Ventricular Failure, and Cardiogenic Shock

Acute MI reduces left ventricular function, leading to acute pulmonary oedema (described above under acute LVF). Cardiogenic shock is the severest form — persistent hypotension with evidence of end-organ hypoperfusion despite adequate volume status. Requires urgent revascularisation (primary PCI), inotropic support, and mechanical circulatory support (intra-aortic balloon pump, Impella).

Chronic Heart Failure

Chronic heart failure (CHF) causes progressive exertional dyspnoea (NYHA classification I–IV), orthopnoea, paroxysmal nocturnal dyspnoea, and ankle oedema. It may have preserved ejection fraction (HFpEF, previously called diastolic heart failure) or reduced ejection fraction (HFrEF, previously called systolic heart failure). BNP/NT-proBNP is the key biomarker; echocardiography is the key imaging investigation. The cornerstone of treatment for HFrEF is the combination of: ACE inhibitor (or sacubitril-valsartan), beta-blocker, mineralocorticoid antagonist (spironolactone), and SGLT2 inhibitor (empagliflozin or dapagliflozin).

Pericarditis and Pericardial Effusion / Tamponade

A large pericardial effusion compresses the heart chambers and reduces cardiac output. Cardiac tamponade — haemodynamically significant pericardial effusion — presents with Beck's triad: hypotension, raised JVP, and muffled heart sounds. Pulsus paradoxus is characteristically present. The ECG may show electrical alternans (alternating amplitude of QRS complexes). Emergency pericardiocentesis is life-saving.

Cardiac Arrhythmia

Rapid tachyarrhythmias (fast AF, SVT, VT) reduce cardiac output and ventricular filling time, causing dyspnoea and palpitations. Bradyarrhythmias (complete heart block, sick sinus syndrome) cause dyspnoea through reduced cardiac output at an inappropriately slow rate.

Haematological Causes

Anaemia

Typical features: Insidious onset of dyspnoea on exertion, fatigue, palpitations, and lightheadedness. Pallor of conjunctiva and palmar creases. The heart must compensate for reduced oxygen-carrying capacity by increasing cardiac output, causing tachycardia, a bounding pulse, and a functional systolic flow murmur.

Causes: Iron deficiency (most common in the UK — menorrhagia, GI blood loss, poor intake); B12 and folate deficiency (macrocytic anaemia); chronic disease; haemolytic anaemia; haematological malignancy.

Key investigation: FBC (haemoglobin, MCV), reticulocyte count, blood film, iron studies, B12 and folate, LDH and bilirubin (if haemolysis suspected).

Endocrine and Metabolic Causes

Thyrotoxicosis

Excess thyroid hormone increases metabolic rate and oxygen demand. Causes dyspnoea, tachycardia, palpitations, heat intolerance, weight loss, and tremor. AF is common. Thyroid function tests (suppressed TSH, elevated free T4 and T3) are diagnostic.

Metabolic Acidosis

Metabolic acidosis stimulates the respiratory centre (via central and peripheral chemoreceptors) to increase ventilation, causing hyperventilation (Kussmaul breathing — deep, sighing respirations). Causes include: diabetic ketoacidosis (DKA), lactic acidosis (sepsis, shock, metformin toxicity), renal tubular acidosis, ingestion of toxins (salicylates, methanol, ethylene glycol). ABG shows low pH, low bicarbonate, elevated anion gap (in most cases).

Diabetic Ketoacidosis (DKA)

DKA occurs in type 1 diabetes (and occasionally type 2 on SGLT2 inhibitors). The severe metabolic acidosis drives Kussmaul breathing. Associated with nausea, vomiting, abdominal pain, polydipsia, polyuria, and a distinctive sweet or fruity breath (from acetone). Treatment: IV fluids, fixed-rate insulin infusion, potassium replacement, identification and treatment of precipitant.

Uraemia

Severe renal failure leads to metabolic acidosis with compensatory hyperventilation. Uraemic pleuritis may cause pleuritic chest pain. Pulmonary oedema from fluid overload is common in end-stage renal disease. Assessment with ABG, FBC, U&E, creatinine.

Musculoskeletal and Mechanical Causes

Large Abdominal Mass

A large intra-abdominal mass (massive ascites, gross hepatosplenomegaly, large ovarian cyst, third-trimester pregnancy, or morbid obesity) elevates the diaphragm and restricts its excursion, reducing tidal volume and causing positional dyspnoea — particularly worse on lying flat. Examination will reveal the abdominal mass.

Thoracic Cage Deformity

Severe kyphoscoliosis — curvature of the spine — can cause marked restriction of chest wall expansion, leading to a progressive restrictive ventilatory defect. Advanced cases develop respiratory failure, right heart failure (cor pulmonale), and may require nocturnal non-invasive ventilation.

Obesity Hypoventilation Syndrome

Morbid obesity (BMI >40) causes exertional dyspnoea through two mechanisms: increased load on the respiratory system, and upper airway collapse during sleep (obstructive sleep apnoea). Obesity hypoventilation syndrome (OHS) — also called Pickwickian syndrome — is defined as daytime hypercapnia (PaCO2 >6 kPa) in obese patients in the absence of another cause. Treatment: weight loss, CPAP or BiPAP nocturnal ventilation.

Neurological Causes

Anxiety and Hyperventilation Syndrome

Typical features: Acute dyspnoea associated with a sensation of inability to take a deep enough breath, tingling in the extremities (perioral and fingertips — from hypocapnia-induced respiratory alkalosis), dizziness, and palpitations. Typically occurs in anxious young patients and in panic attacks. The dyspnoea is often not related to exertion. Spirometry and oxygen saturation are normal.

Discriminating features: ABG during an acute episode: respiratory alkalosis (low PaCO2, high pH, normal PaO2). Response to a rebreathing bag (increasing PaCO2 relieves symptoms) helps distinguish hyperventilation from organic disease, though this manoeuvre should be used carefully.

Management: Reassurance, controlled breathing techniques, management of underlying anxiety disorder. Exclude organic pathology first.

Raised Intracranial Pressure

Raised ICP (from any cause — space-occupying lesion, haemorrhage, hydrocephalus, benign intracranial hypertension) can cause Cheyne-Stokes respiration (cyclical breathing with crescendo-decrescendo pattern and apnoeic periods) through effects on the respiratory centre in the brainstem.

Phrenic Nerve Dysfunction

Phrenic nerve palsy (from cervical spine disease, thoracic malignancy, mediastinal mass, post-cardiac surgery, or idiopathic neuralgia) causes ipsilateral diaphragm paralysis. Bilateral paralysis causes severe orthopnoea (the patient cannot breathe lying flat because both diaphragms are paralysed and abdominal contents compress the lung bases). Assessed with fluoroscopic "sniff test" or ultrasonography of the diaphragm.

Neuromuscular Disease

Dyspnoea from neuromuscular weakness affecting the respiratory muscles. Causes include:

• Muscular dystrophy — progressive respiratory failure as thoracic muscles weaken
• Poliomyelitis — bulbar and respiratory muscle involvement
• Myasthenia gravis — fatigable weakness of respiratory muscles; myasthenic crisis is a medical emergency requiring ICU ventilation
• Guillain-Barré syndrome — ascending motor neuropathy; respiratory failure develops in approximately 25% of patients and may require mechanical ventilation
• Motor neurone disease (ALS) — progressive respiratory muscle weakness with early bulbar involvement

High Altitude Sickness

Acute mountain sickness (AMS) occurs when ascent to high altitude outpaces the body's ability to acclimatise to reduced partial pressure of oxygen. Features: headache, nausea, fatigue, and dyspnoea at altitudes >2500 m. High-altitude pulmonary oedema (HAPE) and high-altitude cerebral oedema (HACE) are severe, potentially fatal forms. Treatment: immediate descent, supplemental oxygen, dexamethasone, acetazolamide, and a portable hyperbaric chamber.