Respiratory Disorders Associated With Sickle Cell Disease
Robyn T. Cohen, MD, MPH
•Sickle cell disease (SCD) affects 100,000 individuals in the United States and is the most common genetic disease among African Americans.
• SCD is caused by a single gene mutation in the β-globin chain of the heme molecule, leading to production of hemoglobin S.
—In a deoxygenated state, hemoglobin S forms polymers that lead to rigid, “sickle-shaped” erythrocytes.
—Increased adhesion, inflammation, and oxidative stress lead to acute vaso-occlusion of the microvasculature, hemolytic anemia, chronic progressive vasculopathy, and eventual end-organ complications.
•SCD is a progressive, life-limiting condition with an average life expectancy in the fifth decade.
•The most severe form, in which patients are homozygous for the HbS mutation, is referred to as sickle cell anemia (SCA).
•Only 1 pharmacological agent is approved by the U.S. Food and Drug Administration to treat SCA: hydroxyurea (hydroxycarbamide).
—A once-daily oral medication that inhibits the production of hemoglobin S and promotes the bone marrow production of fetal hemoglobin
—Well tolerated in infants and children with SCA, with randomized controlled trial–proven benefits seen in children as young as 9 months of age
•Pulmonary abnormalities are common and are associated with an increased risk of death in patients with SCD, but data on prevalence, etiologic origins, and treatment for pulmonary complications are lacking.
Acute Chest Syndrome
•An acute complication of SCD, acute chest syndrome (ACS), is a clinical syndrome characterized by a new pulmonary infiltrate (not atelectasis) accompanied by acute-onset fever and typically associated with oxygen desaturation and respiratory symptoms, including tachypnea, retractions, and shortness of breath.
•It can develop acutely or subacutely, during hospitalization for a vaso- occlusive pain episode, or after a surgical procedure.
•It can progress to respiratory failure, neurological complications, and right-sided heart failure.
•It accounts for 15%–25% of SCD deaths.
•ACS in the preschool age group is associated with increased risk of future ACS episodes.
•The effect of ACS on long-term lung function in children has not been proven, although repeated ACS episodes seem to be associated with decreased lung capacity in adults.
•Although ACS is nonspecific on plain radiographs, typical findings include patchy, scattered air space opacity (Figure 87-1).
—Acute infarction, although rare, demonstrates focal, wedge-shaped opacities.
•Guidelines-based care includes
—Broad-spectrum antibiotics with a cephalosporin and a macrolide
—Pulse oximetry with supplemental O2 as needed
—Monitoring the patient for bronchospasm and acute anemia, with treatment as indicated
Figure 87-1. Frontal radiograph shows acute chest syndrome in a 15-year-old boy with sickle cell disease. Cardiomegaly is also noted.
•Early detection and prevention
—There are no evidence-based biomarkers to predict which patients hospitalized for vaso-occlusive pain episodes will develop ACS.
—Incentive spirometry performed on admission for pain has been shown to reduce the incidence of ACS.