What is the differential diagnosis and initial management for a patient with dyspnea (difficulty breathing) for 2 weeks?

Differential Diagnosis for Dyspnea Present for 2 Weeks

For a patient presenting with dyspnea lasting 2 weeks, the differential diagnosis should focus on the most common life-threatening and treatable cardiopulmonary conditions: acute decompensated heart failure, pneumonia, pulmonary embolism, acute coronary syndrome, COPD exacerbation, asthma exacerbation, pleural effusion, and pneumothorax. 1

Primary Differential Diagnoses by System

Cardiac Causes (Account for ~40% of dyspnea cases)

Heart Failure:

• Acute decompensated heart failure presents with progressive dyspnea, orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema 2
• Patients describe "air hunger" and "inability to get a deep breath" due to restrictive mechanics and elevated filling pressures 1
• Look for jugular venous distention, S3 gallop, bilateral crackles, and peripheral edema on examination 3, 4

Acute Coronary Syndrome:

• Coronary artery disease is the most common cardiac cause when myocardial oxygen supply does not meet demand 2
• Dyspnea may be the anginal equivalent, particularly in diabetics and elderly patients 2

Valvular Disease:

• Mitral stenosis or regurgitation causes elevated left atrial pressures and pulmonary congestion 2
• Aortic stenosis can present with exertional dyspnea even in younger patients with bicuspid valves 2

Arrhythmias:

• Atrial fibrillation with rapid ventricular response causes dyspnea through loss of atrial kick and reduced cardiac output 2
• New-onset tachyarrhythmias or bradyarrhythmias reduce effective cardiac output 2

Pulmonary Causes (Account for ~40% of dyspnea cases)

Infectious:

• Pneumonia presents with fever, productive cough, pleuritic chest pain, and focal crackles 1, 3
• Consider COVID-19, influenza, and bacterial pathogens based on clinical context 3

Obstructive Lung Disease:

• COPD exacerbation presents with increased dyspnea, cough, and sputum production in patients with smoking history 1, 4
• Asthma exacerbation causes "chest tightness" specifically related to bronchoconstriction 1
• Look for wheezing, prolonged expiratory phase, and use of accessory muscles 3, 4

Thromboembolic:

• Pulmonary embolism presents with acute dyspnea, pleuritic chest pain, tachycardia, and hypoxemia 1, 4
• Risk factors include immobilization, malignancy, recent surgery, or hypercoagulable states 4

Pleural Disease:

• Pleural effusion causes compressive atelectasis and stimulation of pulmonary receptors 1
• Pneumothorax presents with sudden-onset dyspnea and pleuritic chest pain with decreased breath sounds 1, 3

Interstitial Lung Disease:

• Presents with progressive dyspnea, dry cough, and bibasilar crackles 1, 4
• Patients describe "air hunger" due to restrictive mechanics 1

Other Important Causes

Anemia:

• Causes dyspnea through reduced oxygen-carrying capacity and compensatory increased cardiac output 3, 5
• Look for pallor, fatigue, and tachycardia 5

Metabolic/Endocrine:

• Metabolic acidosis (diabetic ketoacidosis, uremia) stimulates chemoreceptors causing increased respiratory drive 1
• Thyroid disease can cause dyspnea through multiple mechanisms 4, 6

Psychogenic:

• Panic disorder presents with "sensations of effort, suffocation, and rapid breathing" 1
• Diagnosis of exclusion after ruling out organic causes 3, 4

Initial Diagnostic Approach

First-Line Testing (Perform immediately):

• Complete blood count to assess for anemia or infection 7, 3, 4
• Basic metabolic panel to evaluate for renal dysfunction, electrolyte abnormalities, and acid-base disturbances 7, 3, 4
• Chest radiography to identify pneumonia, heart failure, pleural effusion, pneumothorax, or masses 7, 3, 4
• Electrocardiography to detect ischemia, arrhythmias, or chamber enlargement 7, 2, 3
• Pulse oximetry to assess for hypoxemia requiring supplemental oxygen 7, 3, 4
• Spirometry to identify obstructive or restrictive patterns 7, 3, 4

BNP/NT-proBNP for Heart Failure Evaluation:

• BNP <100 pg/mL or NT-proBNP <125 pg/mL effectively excludes heart failure 1, 2
• Age-stratified cutoffs improve specificity: NT-proBNP <125 pg/mL (age <75) or <450 pg/mL (age ≥75) 1
• Sensitivity of 94-97% and specificity of 81-86% at optimal cutpoints 1

Point-of-Care Ultrasonography (POCUS):

• POCUS added to standard diagnostic pathway leads to statistically significantly more correct diagnoses than standard pathway alone 1
• Improves sensitivity to detect heart failure, pneumonia, pulmonary embolism, pleural effusion, and pneumothorax 1
• Perform lung ultrasound for B-lines (heart failure), consolidation (pneumonia), and pleural effusion 1

Second-Line Testing (If diagnosis remains unclear)

Cardiac Evaluation:

• Echocardiography to assess left ventricular function, valvular disease, right ventricular strain, and pericardial effusion 7, 2, 4
• Stress testing or coronary CT angiography if ischemia suspected 2, 4
• Cardiac MRI for cardiomyopathies or infiltrative diseases when echocardiography inconclusive 2

Pulmonary Evaluation:

• Formal pulmonary function testing to characterize obstructive or restrictive patterns and assess diffusion capacity 7, 4, 8
• High-resolution chest CT for interstitial lung disease, pulmonary embolism, or bronchiectasis 4, 8
• D-dimer testing to help rule out pulmonary embolism (high sensitivity, low specificity) 4
• Ventilation-perfusion scan if CT contraindicated and PE suspected 8

Key Clinical Pearls

Quality of Dyspnea Provides Diagnostic Clues:

• "Chest tightness" is relatively specific for bronchoconstriction (asthma, COPD) 1
• "Air hunger" and "inability to get a deep breath" suggest restrictive mechanics (heart failure, pulmonary fibrosis, dynamic hyperinflation) 1
• "Effort" and "suffocation" are nonspecific but may indicate panic disorder 1

Common Pitfalls:

• History and physical examination alone have high specificity (96%) but low sensitivity (59%) for cardiac causes—do not rely on clinical assessment alone 2
• Normal chest radiography does not exclude cardiac disease, particularly early heart failure or diastolic dysfunction 2
• One-third of patients have multifactorial causes requiring evaluation of multiple organ systems 3, 4
• Clinical presentation alone is adequate for diagnosis in only 66% of cases—maintain low threshold for objective testing 4

When to Refer:

• Specialty referral (pulmonology, cardiology, or multidisciplinary dyspnea clinic) is indicated when diagnosis remains elusive after initial workup 1
• Consider palliative care consultation for refractory dyspnea with limited life expectancy 7