There is a need to treat the multiple causes of ACS.

ACS is a common complication and reason for hospital admission in children with sickle cell disease (SCD). It is also the most common cause of death in this patient population. ACS is defined as a new pulmonary infiltrate, involving at least one complete segment, on chest radiograph and at least one of the following signs or symptoms: (a) chest pain; (b) fever; (c) increased work of breathing (i.e., use of accessory muscles, nasal flaring), tachypnea, cough, or wheeze; or (d) hypoxia.

ACS is the end result of a variety of processes that result in deoxygenation of hemoglobin S and sickling of red blood cells, leading to vaso-occlusion, local ischemia, and vascular damage. Most of the time, the trigger for ACS in an individual patient cannot be identified. However, although infection is the most common identifiable cause for ACS, other important triggers are vaso-occlusive crisis (VOC) and asthma. In fact, many patients who develop ACS have been hospitalized for a different reason, often VOC. Appropriate treatment for ACS targets these multiple etiologies, with the goal of improving oxygenation and, therefore, a reduction in sickling and lung damage.

Initial management of ACS includes antibiotics, fluids and analgesia, and respiratory support, often including bronchodilators. Transfusions are also a mainstay of therapy. Viruses (i.e., respiratory syncytial virus), bacteria (i.e., encapsulated organisms), Mycoplasma and Chlamydia are common infectious agents in acute chest syndrome. Typically, patients are treated empirically with a combination of broad-spectrum antibiotics, such as ceftriaxone (a third-generation cephalosporin) and azithromycin (a macrolide). In more severe cases of ACS, vancomycin is added to cover methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcal pneumoniae.