Table 5.

Comparison of Clinical Features of Recurrent Wheezing vs Asthma in Sickle Cell Disease

Patient Characteristics	Recurrent Intermittent Wheezing	Asthma
Typical asthma symptoms (nocturnal cough, positive family history, atopy, elevated IgE)	•Less frequent71	•Always present72
Potential risk factors	•Increased SCD-related inflammation •Hypovitaminosis D and early acetaminophen exposure93 •Increased hemolysis (elevated LDH)63 •Upper respiratory tract infections •Active or passive smoke exposure	•Upper respiratory tract infections •Active or passive smoke exposure •Hypovitaminosis D and early acetaminophen exposure93 •Increased hemolysis (elevated LDH)63
Pathophysiologic mechanisms	•Hemolysis-driven acute-on-chronic inflammation •Dysregulated arginine-nitric oxide metabolism •Possible altered lung microbiome	•Up-regulation of Th2 cytokines, mast cell- and eosinophil-driven inflammation
Risk for VOE and/or acute chest syndrome	•Increased71, 72	•Increased72
Risk of death	•Increased71	•Increased66
Treatment	Optimal treatment is less clear: •Bronchodilator with inhaled corticosteroid (or leukotriene receptor antagonist) can be useda •For exercise-induced wheezing, pretreatment with bronchodilator •Decreasing hemolysis: Hydroxyurea or chronic transfusions	NIH guidelines: •Bronchodilators, inhaled steroids, and leukotriene receptor antagonists •Consideration of systemic steroids for acute exacerbations

LDH = lactate dehydrogenase; NIH = National Institutes of Health; Th2 = helper T-cell type 2.

^aExpert opinion.