Respiratory and Acute Care Program:
sPLA2 in Sickle Cell Disease
Sickle cell disease is a severe‚ life-shortening hemoglobin disorder. Its hallmark is the deformed‚ sickle–shaped red blood cell that is prone to cause organ damage by occluding small blood vessels [1]. In many patients‚ the course of the disease includes episodes of fever‚ respiratory symptoms‚ and a new lung infiltrate on a chest x–ray‚ a combination termed the acute chest syndrome [2]. The acute chest syndrome is the second most common cause of hospitalization in patients with sickle cell disease‚ and the most common cause of death [1,2]. Patients suffer varying degrees of compromised lung function‚ and may require mechanical ventilation [1]. A variety of triggers‚ including viral infections‚ and painful vascular occlusions in long bones (vaso–occlusive crises‚ VOC)‚ can precede the illness [3]. There are an estimated 10‚000 episodes of acute chest syndrome per year in the U.S. alone‚ and large sickle cell disease populations in the Middle East‚ Europe and Africa [2,4].
Treatment for the acute chest syndrome is mainly supportive (supplemental oxygen‚ etc.)‚ although the sickest patients typically receive transfusions‚ aimed in part at shifting the balance between sickle cells (misshapen and prone to vascular occlusion) and normal red blood cells [1]. Because of antibody formation‚ safe transfusion becomes increasingly difficult to achieve in individual patients. Hydroxyurea has shown efficacy in sickle cell disease‚ but its use is limited by toxicity and variable patient compliance [5]. Based on the severity of the syndrome‚ and the limitations of available therapies‚ a well tolerated preventive therapy has great potential value to patients with sickle cell disease.
A substantial evidence base implicates 
as a contributor to the acute chest syndrome‚
as proposed by Styles‚ et al. at Children’s Hospital Oakland. As shown in the figure (left panel)‚
serum levels are higher in acute chest syndrome than in patients with VOC‚ patients at steady
state (i.e.‚ stable sickle cell disease)‚ or patients with pneumonia [6]. The height of the serum elevation
also reflects the severity of the lung compromise [6].
To investigate the significance of in acute chest syndrome‚ Styles‚ et al. tracked serum
levels in patients presenting with VOC‚ and found that they increased in 4/4 patients in
advance of hospital admission for the onset of acute chest syndrome (Figure‚ right panel) [6]. When
this group further studied as a marker of impending acute chest syndrome (n=21 episodes)‚
they found that the combination of an elevated serum level (above 100 ng/mL) and fever had
a diagnostic sensitivity of 100% and sensitivity of 87% [7]. A second research group also found an
elevation in serum to be a useful warning sign for acute chest syndrome [8].
A further link between and acute chest syndrome was provided by the finding that transfusion
both lowers serum and prevents acute chest syndrome [6]. Regarding the latter‚ in a separate
study 5 of 8 control patients with elevation and VOC developed acute chest syndrome‚ compared
to 0 of 7 patients who received transfusion [9].
The presence of warning signal (elevated level) suggests the possibility of preventing
acute chest syndrome in patients who are at–risk. This is an unusual circumstance‚ in which there
is an opportunity to intervene early in the course of a serious inflammatory disorder‚ in the
prodromal phase. Inhibition of to prevent acute chest syndrome may prove useful both in the
acute setting and as maintenance therapy for patients with sickle cell disease.
For information about the phase 2 IMPACTS trial‚ please visit the IMPACTS Trial Site.