What is the approach to assessing shortness of breath, including definition, classification, differential diagnosis, history, physical examination, investigations, empiric treatment, and indications for referral?

Approach to Assessment of Shortness of Breath

Definition

Dyspnea is a subjective experience of breathing discomfort that varies in intensity, often described as breathlessness or shortness of breath. 1

• Chronic dyspnea is defined as shortness of breath lasting >4 to 8 weeks 1
• Acute dyspnea presents with sudden onset, typically requiring immediate evaluation 2

Classification

By Duration

• Acute: Sudden onset, <4 weeks duration 2
• Chronic: >4-8 weeks duration 1

By Severity

• At rest: Dyspnea present without exertion 1
• With minimal exertion: Walking across room, light housework, dressing 1
• With moderate exertion: Walking distances, climbing stairs 1
• Positional: Orthopnea (lying flat), bendopnea (bending forward within 5-13 seconds) 3

Differential Diagnosis

Primary Categories (85% of cases are cardiac or pulmonary) 1

Cardiovascular (most common with pulmonary):

• Congestive heart failure 1, 2
• Myocardial ischemia/acute coronary syndrome 1
• Valvular heart disease 1
• Pericardial disease 1
• Pulmonary hypertension 1

Pulmonary:

• Chronic obstructive pulmonary disease (COPD) 1
• Asthma and small airways disease 1
• Interstitial lung disease 1
• Pneumonia (viral including COVID-19, bacterial) 4
• Pulmonary embolism 4
• Post-COVID complications 1
• Pleural disease 1

Other Systems:

• Anemia 2
• Chronic kidney disease 1
• Liver disease 1
• Neuromuscular disorders 1
• Obesity (BMI >30) 1
• Deconditioning 5
• Psychiatric/anxiety disorders 1, 2

Note: >30% of cases are multifactorial 1

History

Character of Dyspnea

Essential questions to ask:

• Onset: Sudden vs. gradual 2
• Duration: Days, weeks, or months 1
• Timing: At rest, with exertion, positional 1
• Severity: Distance walked before stopping, flights of stairs climbed 1
• Associated symptoms: Chest pain, cough, fever, leg swelling 1, 4
• Orthopnea: Difficulty breathing lying flat 1
• Bendopnea: Dyspnea within 5-13 seconds of bending forward 3

Red Flags (Immediate Evaluation Required)

• Chest pain with exertion (suggests cardiac ischemia) 1
• Syncope or near-syncope (suggests arrhythmia, pulmonary hypertension, or severe obstruction) 1
• Persistent hypotension 4
• Altered mental status 4
• Respiratory distress (respiratory rate >25, SpO2 <92%, PaO2 <70 mmHg) 1, 4
• Hemoptysis 6
• Unilateral leg swelling (suggests pulmonary embolism) 1, 4

Risk Factors to Assess

Cardiac:

• Hypertension 1
• Diabetes 1
• Atrial fibrillation 1
• Coronary artery disease 1
• Chronic kidney disease 1

Pulmonary:

• Smoking history 1
• Occupational exposures 1
• Recent COVID-19 infection 1
• History of asthma or COPD 1

Thromboembolic:

• Recent surgery or immobilization 4
• Malignancy 4
• Oral contraceptive use 4

Physical Examination (Focused)

Vital Signs

• Respiratory rate (>25 breaths/min is concerning) 1, 4
• Oxygen saturation (SpO2 <92% requires intervention) 1, 4
• Heart rate and blood pressure 7
• Temperature (fever suggests infection) 4

Cardiovascular

• Jugular venous distension (suggests heart failure) 1
• Peripheral edema (legs, abdomen) 1
• Heart sounds: S3 gallop (heart failure), murmurs (valvular disease) 1
• Irregular rhythm (atrial fibrillation) 1

Pulmonary

• Respiratory pattern: Use of accessory muscles, pursed-lip breathing 2
• Auscultation: Wheezing (asthma, COPD), crackles (heart failure, pneumonia, ILD), decreased breath sounds (pleural effusion, pneumothorax) 1, 2
• Percussion: Dullness (effusion, consolidation), hyperresonance (pneumothorax, emphysema) 2

Other

• BMI measurement (obesity contributes to dyspnea) 1
• Signs of anemia: Pallor, tachycardia 2
• Skeletal deformities or diaphragmatic dysfunction 5

Investigations

First-Line (All Patients)

Chest radiography is usually appropriate as the first-line imaging modality 1

• Expected findings: Cardiomegaly (heart failure), infiltrates (pneumonia), hyperinflation (COPD), pleural effusion 1, 4

Pulse oximetry:

• SpO2 <92% at rest or with exertion requires further evaluation 1, 4

ECG:

• Identifies arrhythmias, ischemia, or signs of right heart strain 4

Second-Line Based on Clinical Suspicion

BNP or NT-proBNP (if heart failure suspected):

• BNP >100 pg/mL has sensitivity 0.96, specificity 0.61 for heart failure 1
• NT-proBNP >600 pg/mL (or age-adjusted: 125 pg/mL if <75 years, 450 pg/mL if ≥75 years) suggests heart failure 1
• NT-proBNP ≥160 pg/mL associated with 6-fold increased mortality risk 1

Spirometry (if obstructive or restrictive disease suspected):

• Perform before and after bronchodilator to establish baseline lung function and rule out asthma, COPD, or restrictive disease 5
• If normal and exercise-induced symptoms persist, perform exercise challenge test 5

Chest CT without contrast:

• Usually appropriate or may be appropriate for unclear etiology, suspected COPD, small airways disease, or post-COVID complications 1
• Inspiratory/expiratory CT evaluates air trapping in small airways disease 1

Chest CT with contrast:

• May have role in pleura/chest wall disease or diaphragm dysfunction 1
• Essential if pulmonary embolism suspected 4

Complete blood count:

• Identifies anemia, infection (elevated WBC), or inflammatory processes 4

Inflammatory markers:

• CRP, procalcitonin (if infection suspected) 4

Respiratory pathogen panel:

• Including COVID-19 RT-PCR, influenza, RSV if infectious etiology suspected 4
• Note: COVID-19 RT-PCR has false negatives; multiple samples from different sites increase diagnostic yield 4

Advanced Testing (Selected Cases)

Cardiopulmonary exercise testing (CPET):

• Differentiates true exercise-induced dyspnea from hyperventilation, dysfunctional breathing, or deconditioning 5

Echocardiography:

• Evaluates ejection fraction, valvular disease, pulmonary hypertension, wall thickness 1
• Elevated tricuspid regurgitant velocity (TRV) identifies increased mortality risk 1

Arterial blood gas:

• If hypoxemia or hypercapnia suspected 1

Empiric Treatment

Acute Dyspnea (Based on Most Likely Etiology)

If heart failure suspected (elevated BNP, peripheral edema, crackles):

• Increase diuretic therapy to reduce ventricular filling pressures and volume overload 3
• Optimize afterload reduction with ACE inhibitors, ARBs, or sacubitril/valsartan 3

If COPD/asthma exacerbation suspected (wheezing, known history):

• Bronchodilators (albuterol, ipratropium) 1
• Systemic corticosteroids 1
• Supplemental oxygen to maintain SpO2 >90% 1

If pneumonia suspected (fever, infiltrate on chest X-ray):

• Empiric antibiotics based on local guidelines 4
• Respiratory viral panel including COVID-19 testing 4

If pulmonary embolism suspected (unilateral leg swelling, sudden onset, risk factors):

• Anticoagulation after diagnostic confirmation 4
• Do not dismiss PE based solely on absence of classic symptoms, as pneumonia can mask PE 4

Palliative/Refractory Dyspnea

For refractory dyspnea (numerical rating scale ≥4, especially ≥7):

• Opioids as first-line pharmacological therapy: Morphine 2.5-10 mg PO every 2 hours as needed, or 1-3 mg IV every 2 hours for opioid-naïve patients 3
• Oxygen therapy if SpO2 <92% or for symptom relief at 2-5 L/min (flow rates determined by symptom score, not SpO2) 1
• Hand-held fan before consideration of oxygen therapy 1
• Most benefit occurs within first 24 hours, nearly all improvements within 3 days 1

Indications to Refer

Immediate Emergency Department Referral

• Respiratory distress: Respiratory rate >25, SpO2 <90%, use of accessory muscles 1, 4
• Hemodynamic instability: Persistent hypotension, altered mental status 4
• Suspected pulmonary embolism: Unilateral leg swelling, sudden onset, high clinical suspicion 4
• Acute coronary syndrome: Chest pain with dyspnea, ECG changes 1
• Syncope or near-syncope with dyspnea 1

Cardiology Referral

• Cardiac symptoms or risk factors with abnormal ECG or elevated BNP 5
• Suspected heart failure with preserved ejection fraction (HFpEF score ≥6, echocardiographic abnormalities) 1
• Suspected infiltrative cardiomyopathy (increased LV wall thickness >1.5 cm, carpal tunnel syndrome, lumbar spinal stenosis) 1
• Elevated TRV on echocardiography (suggests pulmonary hypertension) 1

Pulmonology Referral

• Chronic dyspnea of unclear etiology despite initial workup 1
• Suspected interstitial lung disease (crackles, restrictive pattern on spirometry) 1
• Post-COVID complications with persistent dyspnea 1
• Exercise-induced bronchoconstriction requiring specialized testing 5
• Suspected exercise-induced laryngeal dysfunction (inspiratory stridor) requiring flexible laryngoscopy during exercise 5

Hematology Referral

• Suspected sickle cell disease with elevated TRV or NT-pro-BNP ≥160 pg/mL (6-fold increased mortality risk) 1

Critical Pitfalls

Diagnostic Pitfalls

• Assuming all dyspnea with preserved ejection fraction is HFpEF: Must exclude noncardiac mimics (kidney disease, liver disease, chronic venous insufficiency) and cardiac mimics (infiltrative cardiomyopathy, hypertrophic cardiomyopathy, pericardial disease, valvular disease) before diagnosing HFpEF 1

• Dismissing pulmonary embolism based on absence of classic symptoms: Pneumonia can mask PE, particularly when fever predominates; aggressively exclude PE in any patient with subacute dyspnea, especially if symptoms are slow to respond or worsen 4

• Relying on single negative COVID-19 RT-PCR test: False negatives occur; multiple samples from different sites increase diagnostic yield 4

• Diagnosing exercise-induced bronchoconstriction based on self-reported symptoms alone: Requires objective testing with bronchoprovocation challenge; do not initiate therapeutic trials without establishing diagnosis 5

• Ignoring multifactorial etiology: >30% of chronic dyspnea cases have multiple contributing factors; address all identified causes 1

Management Pitfalls

• Measuring TRV during acute illness: TRV may be acutely and transiently increased during vaso-occlusive crisis or acute chest syndrome; perform echocardiography when patient is stable (>4 weeks after hospitalization for acute chest syndrome, >2 weeks after vaso-occlusive crisis) 1

• Using high-flow oxygen in patients at risk for hypercapnia: Consider potential risks when prescribing oxygen at higher flow rates in COPD patients 1

• Failing to reassess oxygen therapy: Oxygen should be reviewed regularly like any pharmacological intervention; most benefit occurs within first 24 hours, nearly all improvements within 3 days 1

• Overlooking psychosocial factors in palliative care: Distress from breathlessness is multi-dimensional; ensure psychosocial factors are assessed and addressed 1

• Inadequate follow-up of chronic dyspnea: Echocardiography every 1-3 years is reasonable for monitoring, as 13% of adults with normal echocardiogram develop elevated TRV after approximately 3 years 1