Can shortness of breath in a young adult of African or Mediterranean descent be caused by sickle cell disease?

Can Shortness of Breath in a Young Adult of African or Mediterranean Descent Be Caused by Sickle Cell Disease?

Yes, shortness of breath (dyspnea) is a well-recognized and clinically significant manifestation of sickle cell disease (SCD) in young adults, particularly those of African or Mediterranean descent, and should prompt urgent evaluation for life-threatening complications such as acute chest syndrome and pulmonary hypertension. 1

Clinical Significance and Mechanisms

Dyspnea in SCD patients occurs through multiple pathophysiologic mechanisms that directly impact morbidity and mortality:

• Acute chest syndrome (ACS) is a leading cause of death in SCD with up to 13% all-cause mortality, and adults characteristically present with shortness of breath, chills, and severe pain (often afebrile), in contrast to younger children who typically present with fever and cough 2, 3

• Pulmonary hypertension develops in SCD patients and is associated with significantly increased mortality risk; the American Thoracic Society specifically includes dyspnea assessment as a critical screening tool, with structured questions about shortness of breath at rest and with minimal exertion 1

• Chronic lung disease progresses through four stages in SCD patients, typically beginning in the second decade of life and ending in death by the fourth decade from pulmonary failure and cor pulmonale; recurrent acute chest syndrome episodes are the strongest predictor (p = 0.0001) of developing this fatal complication 4

Urgent Evaluation Required

When a young adult with known or suspected SCD presents with dyspnea, immediate action is mandatory:

• Emergency transfer to an acute care setting is recommended by the American College of Cardiology (Class I recommendation) for all SCD patients reporting acute chest pain or respiratory symptoms to exclude acute chest syndrome 3, 5

• Baseline oxygen saturation must be obtained immediately with continuous pulse oximetry monitoring, maintaining SpO2 at baseline or ≥96% (whichever is higher) 3, 6

• Chest radiography is essential to identify new pulmonary infiltrates that define ACS (new infiltrate plus fever and/or respiratory symptoms) 6, 7

Structured Dyspnea Assessment

The American Thoracic Society provides specific questions that should be asked when evaluating dyspnea in SCD patients 1:

• Shortness of breath at rest or with minimal exertion (walking across a room, light housework, putting on shoes)
• Distance able to walk before stopping due to dyspnea
• Ability to climb stairs before stopping
• Duration of dyspnea symptoms
• Associated chest pain with exertion
• Orthopnea or difficulty breathing while lying flat
• History of syncope or presyncope
• Leg or abdominal swelling

Risk Stratification

Dyspnea in SCD patients identifies those at substantially elevated mortality risk:

• Elevated tricuspid regurgitant velocity (TRV) on echocardiography identifies patients at higher risk for venous thromboembolic disease, sleep-disordered breathing, and chronic thromboembolic pulmonary hypertension 1

• NT-pro-BNP levels ≥160 pg/ml are associated with a relative risk of death of 6.24 (95% CI, 2.9–13.3) compared to those with lower levels 1

• Echocardiography should be performed every 1-3 years in stable SCD patients (>4 weeks after ACS hospitalization, >2 weeks after vaso-occlusive crisis) 1

Common Pitfalls to Avoid

• Do not dismiss dyspnea as "just a pain crisis" – adults with ACS frequently present with dyspnea and pain together, and ACS has four times higher mortality in adults than children 2

• Do not delay evaluation waiting for fever – adults with ACS are often afebrile, unlike children 2

• Do not attribute all dyspnea to anemia alone – while chronic anemia contributes to baseline dyspnea, acute worsening suggests complications like ACS, pulmonary hypertension, or pulmonary embolism 1

• Do not overlook pulmonary function testing – while routine screening PFT is not recommended for asymptomatic patients, dyspnea at rest or with exertion that is increased compared to baseline warrants diagnostic PFT 1

Population Context

SCD predominantly affects individuals of African, Mediterranean, Middle Eastern, and South Asian descent, with approximately 100,000 individuals living with SCD in the United States and 300,000 infants born annually worldwide with the condition 8, 9. The demographic profile of the patient in question (young adult of African or Mediterranean descent) places them in a high-risk population where SCD should be strongly considered in the differential diagnosis of unexplained dyspnea.