What is the differential diagnosis and initial management for a patient presenting with shortness of breath (SOB), wheezing, and chest pain?

Differential Diagnosis for Shortness of Breath, Wheezing, and Chest Pain

The most critical life-threatening conditions to immediately exclude are acute coronary syndrome (ACS), pulmonary embolism (PE), and acute asthma exacerbation, as these directly impact mortality and require urgent intervention. 1

Immediate Life-Threatening Diagnoses to Exclude

Acute Coronary Syndrome (ACS)

• Chest pain with shortness of breath is a classic presentation of ACS and must be ruled out first 1
• Obtain 12-lead ECG within 10 minutes of first medical contact 1
• Look for ST-segment elevation ≥2mm in contiguous leads (≥2.5mm in men <40 years) 1
• Chest pain may be accompanied by shortness of breath, nausea/vomiting, fatigue, or syncope 1
• Women and older patients (>75 years) are more likely to present with atypical symptoms including primarily shortness of breath rather than chest pain 1
• Initiate ECG monitoring immediately to detect life-threatening arrhythmias 1

Pulmonary Embolism (PE)

• PE commonly presents with chest pain, shortness of breath, and can mimic other cardiopulmonary conditions 1
• Consider PE especially in patients with risk factors (immobility, recent surgery, malignancy, hypercoagulable states) 1
• CTA chest with IV contrast is the gold standard for diagnosis 1
• Chest radiography is neither sensitive nor specific but often performed as baseline investigation 1

Acute Asthma Exacerbation

• Defined as acute or subacute worsening of symptoms (cough, wheeze, chest tightness, dyspnea) with increased need for rescue medications 1
• Assess pulse rate, respiratory rate, degree of breathlessness, use of accessory muscles, amount of wheezing, level of consciousness 1
• Pulse oximetry is essential; hypoxemia defined as oxygen saturation <90-92% 1
• Peak expiratory flow (PEF) monitoring helps assess severity 1
• Risk factors include: poor asthma control, underuse/poor adherence to treatment, aspirin/NSAID use, comorbidities 1

Other Important Respiratory Causes

Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

• Progressive increase in shortness of breath, cough, wheeze that doesn't respond to usual bronchodilator therapy 1
• Patients may have small-airway dysfunction with increased ventilatory requirements during exertion 1
• Manage with inhaled corticosteroids and beta-agonists; avoid anticholinergics if excessive secretions present 1

Exercise-Induced Bronchoconstriction (EIB)

• Wheezing and shortness of breath triggered by physical exertion 1
• Requires objective testing to differentiate from other causes 1
• Bronchoprotective therapy administered minutes to hours before exercise 1

Pneumonia/Respiratory Infection

• May present with wheezing, shortness of breath, chest pain, and fever 2
• End-expiratory wheezes may be present 2
• Consider healthcare-associated pneumonia in appropriate clinical context 2

Airway Obstruction (Foreign Body, Mass)

• Can mimic COPD exacerbation or pneumonia with persistent wheezing despite treatment 2
• Consider if symptoms are slow to respond to standard therapy 2
• CT chest and bronchoscopy may be needed for diagnosis 2

Cardiac Causes Beyond ACS

Heart Failure with Preserved Ejection Fraction (HFpEF)

• Presents with shortness of breath and may have wheezing ("cardiac asthma") 3
• Consider diastolic stress echocardiography in patients with unexplained dyspnea 3
• Symptoms can mimic or coexist with respiratory limitations 3

Coronary Artery Disease (Stable Angina)

• Chest pain provoked by stress (physical or emotional) 1
• May present with associated shortness of breath 1
• Requires risk stratification and pretest probability assessment 1

Gastrointestinal Causes

Gastroesophageal Reflux Disease (GERD)

• Can cause chest pain and respiratory symptoms including wheezing 1
• Exercise-onset GERD may be misdiagnosed as asthma 1
• Trial of proton pump inhibitors may help differentiate, though evidence is mixed 1
• In low-risk chest pain patients, GERD exceeds CAD by almost 10-fold 1

Psychological/Functional Causes

Anxiety Disorders and Hyperventilation

• Common in low-risk patients with chest pain, shortness of breath, and normal cardiac workup 1
• Depression and anxiety each exceed CAD by almost 10-fold in low-risk chest pain patients 1
• Refer for psychological evaluation when symptoms suggest hyperventilation or anxiety disorders 1
• Cognitive-behavioral therapy shows 32% reduction in chest pain frequency 1

Vocal Cord Dysfunction (VCD)

• Can present with wheezing and shortness of breath without true bronchoconstriction 1
• Requires differentiation through objective testing 1

Other Systemic Causes

Pulmonary Vascular Disease

• Chronic thromboembolic pulmonary hypertension (CTEPH) can cause progressive dyspnea and chest pain 1
• Consider in patients with persistent symptoms after acute PE 1

Connective Tissue Disease (e.g., Sjögren's)

• Interstitial lung disease presents with shortness of breath, cough, and chest pain 1
• Airways disorder may include asthma/COPD-like symptoms with wheezing 1
• Bronchiectasis and small airway disease can occur 1

Anemia, Obesity, Hyperthyroidism

• Systemic disorders causing breathlessness without primary lung pathology 1

Neuromuscular Disease

• Diaphragm failure can present with dyspnea 1

Initial Management Algorithm

1. Immediate assessment: Vital signs, oxygen saturation, 12-lead ECG 1
2. Rule out life-threatening causes first: ACS, PE, severe asthma exacerbation 1
3. Obtain chest radiography as baseline investigation 1
4. Perform spirometry when stable to differentiate obstructive vs restrictive patterns 1
5. Consider cardiac biomarkers if ACS suspected 1
6. Assess response to bronchodilators if wheezing present 1
7. If initial workup negative and symptoms persist, consider GERD, psychological factors, or less common causes 1

Critical Pitfalls to Avoid

• Do not rely on nitroglycerin response as a diagnostic maneuver for ACS; it can be misleading 1
• Do not assume typical presentation: Women, elderly, and patients with diabetes may present atypically with predominantly dyspnea rather than chest pain 1
• Do not overlook psychological factors in patients with recurrent presentations and negative workups 1
• Do not miss airway obstruction from foreign body or mass if symptoms fail to respond to standard therapy 2
• Recognize that multiple conditions can coexist (e.g., asthma with GERD, cardiac disease with anxiety) 1