What is the differential diagnosis and management approach for a patient presenting with shortness of breath?

Differential Diagnosis and Management of Shortness of Breath

Immediate Assessment and Stabilization

Begin with ABC assessment, pulse oximetry (mandatory—never omit), and start oxygen therapy immediately if SpO2 <94% (target 94-98% for most patients, 88-92% for COPD risk). 1

• Record vital signs including pulse rate, respiratory rate, and continuous oxygen saturation monitoring until stable 1
• Do not delay oxygen therapy waiting for formal prescription—give immediately in emergencies with documentation afterward 1
• Obtain brief focused history regarding onset (acute <4 weeks vs chronic >4-8 weeks), duration, associated symptoms (orthopnea, paroxysmal nocturnal dyspnea, fever, chest pain, cough), and risk factors (hypertension, diabetes, smoking, atrial fibrillation) 2, 3

Essential Initial Diagnostic Testing

Obtain BNP or NT-proBNP level as the single most important test—this has 96-99% sensitivity for ruling out heart failure when BNP <100 pg/mL. 1

• Order chest X-ray for all patients to identify cardiomegaly, pulmonary congestion, infiltrates, pleural effusion, or hyperinflation 2, 3
• Obtain arterial blood gas if SpO2 <92% or COPD/hypercapnia suspected 1
• Perform electrocardiography to screen for cardiac ischemia, arrhythmias, and right heart strain 3
• Clinical assessment alone has high specificity (96%) but low sensitivity (59%) for cardiac causes—biomarker testing is essential 1

Algorithmic Diagnostic Approach Based on BNP Results

If BNP ≥100 pg/mL or NT-proBNP ≥300 pg/mL (Cardiac Cause Likely):

Proceed immediately to echocardiography to assess left ventricular ejection fraction, diastolic function, valvular abnormalities, right ventricular function, and pulmonary hypertension. 2, 1

If BNP <100 pg/mL (Non-Cardiac Cause Likely):

Perform spirometry to differentiate obstructive from restrictive patterns—this is mandatory before prescribing inhalers. 3

• Spirometry combined with chest X-ray findings will identify most pulmonary causes 3
• Consider peak expiratory flow in suspected asthma to assess airflow obstruction severity 1
• If resting tests are normal, consider cardiopulmonary exercise testing (CPET) to distinguish cardiac, pulmonary, and deconditioning causes 1

Differential Diagnosis by Clinical Presentation

Acute Onset (<4 weeks):

• Pulmonary embolism: Consider D-dimer testing to help rule out 2, 3
• Pneumothorax: Identified on chest X-ray 3
• Acute heart failure: Elevated BNP with orthopnea/paroxysmal nocturnal dyspnea 2
• Pneumonia: Fever, infiltrates on chest X-ray, consider COVID-19 testing 2

Chronic Onset (>4-8 weeks):

• COPD: Smoking history, hyperinflation on chest X-ray, obstructive pattern on spirometry 2, 3
• Interstitial lung disease: Smoking history, restrictive pattern on spirometry, may require CT chest 2, 3
• Chronic heart failure: Risk factors (hypertension, diabetes, atrial fibrillation), elevated BNP 2
• Asthma: Reversible airflow obstruction on spirometry 3

Disease-Specific Management

Heart Failure (BNP elevated, echocardiography confirms):

Increase diuretic therapy and optimize afterload reduction with ACE inhibitors or ARBs; admit for severe symptoms. 2

COPD/Asthma Exacerbation:

Administer bronchodilators, systemic corticosteroids, supplemental oxygen, and antibiotics if bacterial infection suspected. 2

Pneumonia:

Start broad-spectrum antibiotics, provide supplemental oxygen, and consider COVID-19 testing. 2

Dyspnea in Advanced Cancer:

Opioids are the only pharmacological agents with sufficient evidence for palliation of dyspnea—they can be used without causing relevant respiratory depression. 4

• Treat reversible causes when consistent with patient's performance status and goals of care 4
• Implement non-pharmacological interventions: cooling the face, opening windows, small ventilators, adequate positioning (coachman's seat, elevation of upper body), respiratory training 4
• Provide education to patient and family about simple measures to reduce helplessness and anxiety 4

Indications for Specialist Referral

Cardiology Referral:

Refer for cardiac symptoms/risk factors with elevated BNP, suspected HFpEF, elevated tricuspid regurgitation velocity, or severe valvular disease. 2

Pulmonology Referral:

Refer for chronic dyspnea of unclear etiology despite initial workup, suspected interstitial lung disease, post-COVID complications, or symptoms not responding to standard COPD/asthma therapy. 2, 3

Sleep Medicine Referral:

Refer for nocturnal awakening with gasping, witnessed apneas, or excessive daytime sleepiness suggesting obstructive sleep apnea. 3

Critical Pitfalls to Avoid

• Never rely on clinical assessment alone without biomarker testing 1
• Never omit pulse oximetry—this is mandatory in all breathless patients 1
• Do not prescribe inhalers without spirometry confirmation 3
• Remember that >30% of cases are multifactorial, requiring evaluation across multiple systems 3
• Recognize that TRV measurement in sickle cell disease should only be performed when patient is stable (>4 weeks after acute chest syndrome, >2 weeks after vaso-occlusive crisis) 4