sPLA2 in EBC During Acute Chest Syndrome

The purpose of this research study is to test the ease and effectiveness of collecting
exhaled breath condensate (liquid) to measure levels of a biomarker, secretory phospholipases
A2 (sPLA2) in people with sickle cell disease during an attack of acute chest syndrome. sPLA2
levels have been reported to be much higher in persons with acute chest syndrome and might be
useful to diagnose and to evaluate the effects of therapy.

Serial monitoring of plasma sPLA2 levels might lead to earlier or more accurate detection of
acute chest syndrome and monitoring of its progression or improvement in patients with sickle
cell disease. However, there is a significant inherent risk of frequent blood collection
further dropping the blood (hemoglobin) levels of an already anemic patient. If sPLA2 can be
measured in exhaled breath condensate, this non-invasive and well-tolerated sample collection
might allow for serial monitoring of the enzyme without depleting the patient's already
diminished blood supply.

Inclusion Criteria:

1. Diagnosis of sickle cell anemia (the most severe types of sickle cell disease) as
demonstrated by one of the following genotypes: HbSS, HbSβ0

2. Age ≥ 7 and < 40 years

3. Diagnosis of ACS as defined below

4. EBC collection able to be initiated within 48 hours of diagnosis of ACS

Definition of acute chest syndrome to be used: New radiographic pulmonary infiltrate of at
least one complete lung segment in addition to 2 or more of the following symptoms: fever,
chest pain, dyspnea, tachypnea, hypoxia. Given the small number of subjects in this
feasibility study, we are using the more conservative definition in order to ensure samples
are from patients with true ACS. This will increase the likelihood that sPLA2 levels will
be high enough for measurement.

Exclusion Criteria:

1. Blood product transfusion in the previous 3 months (due to potential alterations in
biomarkers, including sPLA2)

2. Chronic inflammatory conditions other than sickle cell (due to elevation from baseline
of sPLA2 in inflammatory conditions)

3. Physical inability to correctly breathe into the mouthpiece for the required amount of
time without compromising respiratory status

4. Intubated patients (though EBC can be measured in intubated patients, we will not
include this subpopulation for the purpose of this study)

5. Pregnancy (due to the hematologic and respiratory changes that physiologically occur
during gestation)