Acute chest syndrome of sickle cell disease: new light on an old problem

The pulmonary findings of acute chest syndrome of sickle cell disease have been well characterized in numerous studies. Whereas a third of patients have a documented infection associated with this syndrome, and fat embolism from necrotic marrow is the etiologic factor in another approximately 10%, no cause is discovered in the majority of patients. In most patients, however, the underlying pathophysiology is the presence of a hypoxia-driven, adhesion-related occlusive event in the pulmonary microcirculation. This may be accompanied by a decrease in the levels of normal cytoprotective and anti-adhesive mediators such as nitric oxide. In the patient with sickle cell disease, the lung is also a uniquely vulnerable target organ because its vasculature constricts with hypoxia in contrast to other vascular beds. This review will establish the links between known etiologic agents and the pathophysiology of this syndrome. An additional section of this review will deal with experimental therapies. The use of inhaled nitric oxide will be explored in depth because advances in this area are current and uniquely relevant to acute chest syndrome.