What is the differential diagnosis for a 61-year-old female experiencing shortness of breath (SOB) with exertion, arm stiffness, and chest tightness that can be reproduced by cold air, and is asymptomatic at rest?

Differential Diagnosis for Exertional Dyspnea with Cold Air Provocation

The most likely diagnoses in this 61-year-old woman are exercise-induced bronchoconstriction (EIB) or stable coronary artery disease (SCAD), with cold air provocation strongly suggesting either asthma-related airway hyperreactivity or coronary vasospasm. 1, 2

Primary Diagnostic Considerations

Exercise-Induced Bronchoconstriction (EIB)

• Chest tightness provoked by cold air is a hallmark feature of EIB, as cold air is a potent trigger for bronchospasm in susceptible individuals 1
• The pattern of symptoms only with exertion and resolution at rest is classic for EIB 2
• "Tightness" is the dominant sensation during bronchoconstriction and arises from pulmonary afferents rather than work-related sensations 1
• Cold air specifically triggers bronchoconstriction through airway cooling and drying mechanisms 1

Stable Coronary Artery Disease (SCAD)

• At age 61, cardiac ischemia must be excluded given the chest tightness with exertion that resolves at rest 1
• The European Society of Cardiology defines typical angina as substernal chest discomfort provoked by exertion and relieved by rest within minutes 1
• Cold weather is a classical exacerbating factor for angina 1
• Shortness of breath may be the sole symptom of SCAD and can be difficult to differentiate from pulmonary causes 1
• Atypical angina in women may present with chest tightness triggered by exertion without classic crushing pain 1

Exercise-Induced Laryngeal Dysfunction (EILD)

• Should be considered if inspiratory stridor is present, though not mentioned in this case 1, 2
• Can coexist with EIB and requires flexible laryngoscopy during exercise for definitive diagnosis 1

Chronic Obstructive Pulmonary Disease (COPD)

• Less likely given symptoms only with exertion, but smoking history should be assessed 1
• Interestingly, cold air can actually reduce breathlessness in COPD patients by inducing relative hypoventilation, opposite to the effect in asthma 3

Deconditioning/Reaching Physiological Limit

• Common cause of exertional dyspnea but would not explain cold air provocation or chest tightness 4
• Arm stiffness could suggest poor conditioning or musculoskeletal issues 4

Recommended Diagnostic Algorithm

Step 1: Initial Objective Testing

• Perform spirometry before and after bronchodilator to establish baseline lung function and rule out underlying asthma or COPD 2
• Obtain ECG to assess for cardiac ischemia, arrhythmias, or conduction abnormalities 1, 5
• Measure blood pressure and assess cardiovascular risk factors including lipids and glucose 1

Step 2: Exercise Challenge Testing (if spirometry normal)

• Conduct exercise challenge test using treadmill or cycle ergometry, as indirect challenges are more sensitive than methacholine for diagnosing EIB 2
• Patient must achieve and sustain heart rate ≥85% of maximum for adults during the test 1, 2
• Measure spirometry at baseline, immediately post-exercise, and at 5,10,15-minute intervals to detect delayed bronchoconstriction 2
• A fall in FEV1 ≥10% from baseline confirms EIB 1

Step 3: Cardiac Evaluation (if high suspicion or risk factors present)

• Refer for cardiopulmonary testing and cardiology evaluation if cardiac symptoms or risk factors exist 1, 2
• Consider stress testing or coronary imaging based on pretest probability 1
• The combination of age, exertional symptoms, and cold air provocation warrants cardiac workup even if pulmonary testing is positive 1

Step 4: Advanced Testing if Initial Workup Negative

• Perform cardiopulmonary exercise testing (CPET) to differentiate true exercise-induced dyspnea from hyperventilation, dysfunctional breathing, or deconditioning 2, 4
• Consider flexible laryngoscopy during exercise if EILD is suspected 1, 2

Critical Pitfalls to Avoid

• Do not diagnose based on self-reported symptoms alone—objective testing with bronchoprovocation or cardiac stress testing is mandatory 2
• Do not initiate therapeutic trials without establishing a diagnosis, as this leads to unnecessary medication use and missed alternative diagnoses 2
• Do not assume pulmonary cause in a 61-year-old woman with exertional chest tightness without excluding cardiac ischemia first, as women often present with atypical angina 1
• Recognize that cold air can worsen asthma but paradoxically improve COPD symptoms, helping differentiate these conditions 3
• Be aware that chest tightness from bronchoconstriction differs from work/effort sensations and responds more rapidly to bronchodilators 1

Additional Clinical Considerations

• Arm stiffness may represent musculoskeletal deconditioning, peripheral vascular disease, or referred cardiac pain and requires specific assessment 1
• If EIB is confirmed, prescribe inhaled short-acting β2-agonists for protection before exercise, but caution against daily use due to tolerance development 1
• Schedule regular follow-up visits as medications can differ in effectiveness over time due to environmental conditions and exercise intensity 1
• Consider exercise-induced anaphylaxis if systemic symptoms like pruritis, urticaria, or hypotension accompany respiratory symptoms 1, 2