What is the approach to evaluating and managing a patient with shortness of breath, considering various differentials and potential underlying conditions?

Approach to Shortness of Breath: Systematic Evaluation and Key Differentials

Begin with spirometry and chest radiography as your first-line diagnostic tests, as these objective measures are essential to differentiate between cardiac, pulmonary, and other causes of dyspnea before initiating any treatment. 1, 2

Initial Clinical Assessment

Critical Historical Elements

• Onset and timing distinguish acute from chronic causes: acute onset (<4 weeks) suggests pulmonary embolism, pneumothorax, or acute heart failure, while chronic dyspnea (>4-8 weeks) points toward COPD, interstitial lung disease, or chronic heart failure 1, 2
• Associated symptoms provide diagnostic clues: orthopnea and paroxysmal nocturnal dyspnea indicate cardiac causes (particularly heart failure), while fever with productive cough suggests pneumonia 2
• Risk factor assessment is mandatory: smoking history points to COPD or interstitial lung disease, while hypertension, diabetes, and atrial fibrillation increase likelihood of heart failure 2

Physical Examination Priorities

• Cardiovascular signs: jugular venous distention, peripheral edema, and hepatomegaly suggest heart failure 3
• Respiratory findings: wheezing indicates airway obstruction (asthma/COPD), while decreased breath sounds may indicate pleural effusion or pneumothorax 4
• Restrictive indicators: obesity, skeletal defects (pectus excavatum), or signs of diaphragmatic dysfunction suggest restrictive lung conditions 1

Systematic Differential Diagnosis Framework

Six Major Categories to Consider

The European Respiratory Journal emphasizes that breathlessness stems from six primary categories 1:

1. Lung disease (COPD, asthma, interstitial lung disease, pneumonia)
2. Heart disease (heart failure, myocardial ischemia, valvular disease)
3. Pulmonary vascular disease (pulmonary embolism, pulmonary hypertension)
4. Neuromuscular disease (diaphragm failure, myasthenia gravis)
5. Systemic disorders (anemia, obesity, hyperthyroidism)
6. Psychogenic factors (anxiety, hyperventilation syndrome)

More than 30% of cases are multifactorial, requiring evaluation across multiple systems. 1

Essential Diagnostic Testing Algorithm

First-Line Investigations (All Patients)

• Chest radiography: identifies cardiomegaly, pulmonary congestion, infiltrates, pleural effusion, and hyperinflation 1, 2
• Spirometry: differentiates obstructive from restrictive patterns and is mandatory before prescribing inhalers 1, 5
• Electrocardiography: screens for cardiac ischemia, arrhythmias, and right heart strain 2, 3
• Complete blood count and basic metabolic panel: identifies anemia and metabolic derangements 2, 4

Second-Line Testing Based on Clinical Suspicion

For Suspected Cardiac Causes

• BNP or NT-proBNP: obtain in all patients with acute dyspnea to distinguish cardiac from non-cardiac causes; use cutoffs of BNP >100 pg/mL or NT-proBNP >300 pg/mL to proceed with echocardiography 2
• Echocardiography: essential for assessing left ventricular ejection fraction, diastolic function, valvular abnormalities, and right ventricular function 2

For Suspected Pulmonary Causes

• Chest CT without contrast: second-line option for COPD, small airways disease, and post-COVID complications 1
• Inspiratory/expiratory CT: evaluates air trapping in small airways disease 1
• Pulmonary function testing: comprehensive evaluation when spirometry suggests restrictive or mixed patterns 4

For Exercise-Induced Dyspnea

• Exercise challenge testing: perform indirect challenges (exercise, EVH, or mannitol) rather than direct methacholine challenges, as they are more sensitive for exercise-induced bronchoconstriction 1, 6
• Cardiopulmonary exercise testing (CPET): differentiates true exercise-induced dyspnea from hyperventilation, dysfunctional breathing, or deconditioning 1, 6

Critical Pitfalls to Avoid

Do Not Prescribe Inhalers Without Objective Testing

A substantial proportion (28.4%) of patients treated with inhalers for presumed obstructive airway disease have no evidence of lung disease on proper testing. 5 This highlights the danger of empiric treatment without spirometry confirmation.

Recognize Obstructive Patterns May Not Always Be Asthma/COPD

• Obstructive spirometry with cough, wheeze, and breathlessness could represent localized central airway narrowing from bronchial carcinoma, foreign body, or post-tracheostomy stenosis rather than generalized airway disease 1, 7
• Always consider CT chest if symptoms don't respond appropriately to standard therapy 7

Don't Miss Exercise-Induced Anaphylaxis

• Consider exercise-induced anaphylaxis (not just bronchoconstriction) when respiratory symptoms are accompanied by systemic manifestations like pruritus, urticaria, or hypotension 1
• Food-dependent exercise-induced anaphylaxis (particularly wheat-related) requires avoiding exercise 4-6 hours after specific food ingestion 1

Specialist Referral Indications

Cardiology Referral

• Cardiac symptoms or risk factors with elevated BNP 2
• Suspected heart failure with preserved ejection fraction (HFpEF) 2
• Elevated tricuspid regurgitation velocity or severe valvular disease 2

Pulmonology Referral

• Chronic dyspnea of unclear etiology despite initial workup 2
• Suspected interstitial lung disease 2
• Post-COVID complications with persistent dyspnea 1, 2
• Symptoms not responding to standard COPD/asthma therapy 2
• Need for bronchoscopy or advanced pulmonary function testing 4

Sleep Medicine Referral

• Nocturnal awakening with gasping, witnessed apneas, or excessive daytime sleepiness suggesting obstructive sleep apnea 3

Special Considerations for Specific Populations

Athletes and Exercise-Related Dyspnea

• Perform eucapnic voluntary hyperpnea (EVH) as the preferred surrogate challenge in athletes without current asthma history 1
• Ensure adequate challenge intensity: ventilation ≥60% of maximum voluntary ventilation, or heart rate ≥85% of maximum in adults (≥95% in children and elite athletes) 1
• Consider flexible laryngoscopy during exercise to diagnose exercise-induced laryngeal dysfunction (EILD) when inspiratory stridor is present 1, 6

Obese Patients

• Dyspnea in obesity is strongly associated with increased oxygen cost of breathing without bronchoconstriction 1
• Consider restrictive physiology and perform detailed pulmonary examination 1