What is the best management approach for a smoker with exertional dyspnea (shortness of breath on exercise), normal stress test and Pulmonary Function Test (PFT) results, and a history of resolved hematuria?

Management of Exertional Dyspnea in a Smoker with Normal Stress Test and PFTs

This patient requires cardiopulmonary exercise testing (CPET) to identify the underlying cause of exertional dyspnea, as normal resting pulmonary function tests and stress testing do not exclude exercise-induced pathology, deconditioning, or dysfunctional breathing patterns. 1

Immediate Diagnostic Approach

Rule Out Occult Cardiac Disease

• Obtain B-type natriuretic peptide (BNP) or NT-proBNP level as the single most important next test, since a BNP <100 pg/mL has 96-99% sensitivity for ruling out heart failure 2
• If BNP is elevated (≥100 pg/mL), proceed to echocardiography to assess for heart failure with preserved ejection fraction (HFpEF), diastolic dysfunction, or pulmonary hypertension 2
• Standard stress testing may miss HFpEF and pulmonary vascular disease, which are common causes of exertional dyspnea with normal resting cardiac function 3

Perform Cardiopulmonary Exercise Testing (CPET)

• CPET is the definitive test to differentiate between cardiac limitation, pulmonary gas exchange abnormalities, deconditioning, and dysfunctional breathing when resting tests are normal 1, 2
• CPET can identify exercise-induced arterial desaturation, ventilation-perfusion mismatch, chronotropic insufficiency, and early ventilatory limitation not apparent on resting PFTs 3
• This is particularly important in smokers, as 50% of current or former smokers with preserved pulmonary function (normal spirometry) still have respiratory symptoms, activity limitation, and evidence of airway disease 4

Consider Exercise-Induced Bronchoconstriction (EIB)

Diagnostic Testing for EIB

• Perform an exercise challenge test using treadmill or cycle ergometry, achieving heart rate ≥85% of maximum for 6 minutes after a 2-4 minute warm-up 3, 1
• Measure spirometry at baseline, immediately post-exercise, and at 5,10, and 15-minute intervals to detect delayed bronchoconstriction 1
• Normal resting PFTs do not exclude EIB, which is the most common pathologic cause of exercise-related dyspnea in young adults 1
• Do not diagnose based on self-reported symptoms alone or initiate therapeutic trials without objective testing 3, 1

Alternative Bronchoprovocation Testing

• If exercise challenge is not feasible, consider graded challenge with inhaled mannitol or eucapnic voluntary hyperpnea (EVH) as surrogate tests 3

Evaluate for Non-Pulmonary Causes

Screen for Exercise-Induced Laryngeal Dysfunction (EILD)

• If inspiratory stridor is present or suspected, perform flexible laryngoscopy during exercise to diagnose EILD 3, 1
• EILD can masquerade as asthma and requires different management (vocal exercises rather than bronchodilators) 3, 5

Assess for Deconditioning and Dysfunctional Breathing

• Many patients with exertional dyspnea are simply reaching their physiological limit due to deconditioning or have functional dysfunctional breathing patterns 5
• CPET can distinguish true exercise-induced dyspnea from hyperventilation, dysfunctional breathing, or deconditioning 1
• These conditions require reassurance, advice, breathing retraining, and exercise rehabilitation rather than pharmacotherapy 5

Address Smoking-Related Airway Disease

Recognize Symptomatic Smokers with Preserved Spirometry

• Symptomatic current or former smokers with normal spirometry have higher rates of respiratory exacerbations (0.27 vs 0.08 events per year), greater activity limitation, and evidence of airway-wall thickening on CT compared to asymptomatic smokers 4
• These patients do not meet current COPD criteria but have clinically significant disease requiring intervention 4

Initiate Smoking Cessation and Pulmonary Rehabilitation

• Refer to pulmonary rehabilitation program, which decreases nicotine dependence, daily cigarette consumption, and improves dyspnea scores even in active smokers 6
• Pulmonary rehabilitation improves FEV1, PaO2, 6-minute walk distance, and quality of life in both active and former smokers 6
• Smoking cessation is the single most important intervention to prevent progression of airway disease 3

Address the History of Hematuria

Ensure Appropriate Urologic Follow-Up

• While the hematuria has resolved, smokers with a history of hematuria require urologic evaluation to exclude bladder cancer or other malignancy
• This is a separate issue from the dyspnea but must not be overlooked in the overall management plan

Common Pitfalls to Avoid

• Do not assume normal resting PFTs exclude all pulmonary pathology—exercise testing is required to identify exercise-induced abnormalities 1
• Do not rely on clinical assessment alone for cardiac causes—it has high specificity (96%) but low sensitivity (59%), making biomarker testing essential 2
• Do not initiate bronchodilator therapy without objective evidence of bronchospasm—42% of symptomatic smokers with preserved spirometry use bronchodilators without evidence base 4
• Do not overlook the possibility of reaching physiological limit or dysfunctional breathing—these are common causes requiring non-pharmacologic interventions 5