Role of Placenta Growth Factor in Sickle Acute Chest Syndrome

The proposed research is a clinical study designed to test the hypothesis that PlGF levels in
blood at baseline in patients with SCD will correlate with leukotriene (LT) levels and will
be reflective of the degree of airway obstruction; and that acute elevations in PlGF levels
will occur during an acute sickle event and precede clinical and radiological recognition of
ACS. This is a biological study that does not fall into the criteria of a phase I-IV trial.

Measurements will be done at two stages. First, patients who are admitted to the hospital
with an acute sickle event will have a daily evaluation for the first 4 days of the admission
or up until the patient has an ACS event. Measurements of inpatient spirometry (at primary
site only) and impulse oscillometry will be performed daily. Measurements on 35 ACS events
with ACS developing on the 3rd/4th day of admission will be collected. Measurements on
patients developing ACS will be compared to those who do not develop ACS will allow for
earlier prediction of ACS. Finally, patients who have an ACS or admission for an acute
sickling event will be evaluated again after 3-4 weeks in order to get a baseline
measurement. One hundred baseline measurements will be made. Twenty of these baseline
patients will also have one or two additional baseline evaluations at subsequent clinic
visits to evaluate the overall non-event baseline distribution and intra-subject baseline
variability. Patients will have measurements repeated if admitted for an acute event greater
than one year since the last baseline measurement . These measurements will be used to see if
there is any prognostic information for a subsequent acute or ACS event. Some patients may
only have baseline data collected.

Inclusion criteria:

1. Patients must have a diagnosis of SCD (HbSS, HbSC or HbS beta/thal) by hemoglobin
electrophoresis or gene mapping. Very few patients with HbSC or HbS beta/thal would go
onto develop ACS, but they will serve as important controls.

2. Patients must be ≥5.5 years of age and ≤30 years of age.

3. Patients must be able to comply with pulmonary function tests.

Exclusion criteria:

1. Patients taking anti-leukotriene medications such as montelukast (Singulair®) or
zileuton (Zyflo®) 30 days prior to enrollment will be ineligible, although patients
with SCD and asthma who are not on leukotriene inhibitors will be eligible.

2. Patients with known congenital heart disease or with congenital lung
abnormality/disease that will affect the pulmonary function testing and methacholine
challenge testing will be ineligible (examples include patients with cyanotic heart
disease, immotile cilia syndrome, cystic fibrosis, diaphragmatic hernia).

3. Any patient with neurologic abnormalities, stroke, developmental delay, or other
medical condition that would preclude cooperation with pulmonary function testing or
compliance with protocol procedures will be ineligible.

4. Patients over 30 years of age will be ineligible.

5. Patients who are pregnant or nursing.

6. Patients on chronic transfusions will be ineligible.

- If patients come off transfusion therapy, they will be eligible 3 months
following the last transfusion.

- Patients receiving simple transfusions will be eligible, but baseline
measurements will be made 3 months following the simple transfusion.