Sickle Cell Disease, Acute Chest Syndrome
Conditions
Keywords
acute chest syndrome, secretory phospholipases A2, exhaled breath condensate, sickle cell disease
Brief summary
Secretory phosholipases A2 (sPLA2) are significantly elevated in the plasma of sickle cell disease patients with acute chest syndrome (ACS), and similar enzymes have been measured in exhaled breath condensate (EBC), which is collected easily and non-invasively. The investigators hypothesize that sPLA2 will be measurable in EBC samples from sickle cell patients with acute chest syndrome.
Detailed description
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.
Interventions
DIAGNOSTIC_TESTExhaled Breath Condensate (EBC)
Serial EBC samples will be collected within 48 hours of acute chest syndrome (ACS) diagnosis and at 2 week follow up
DIAGNOSTIC_TESTPlasma Sample
Serial plasma samples will be collected within 48 hours of acute chest syndrome (ACS) diagnosis and at 2 week follow up
Sponsors
Virginia Commonwealth University
Study design
Observational model
CASE_ONLY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
7 Years to 30 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| sPLA2 Measurement in EBC during ACS | Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission) | sPLA2 level in EBC at Time point 1 (during acute ACS episode) as measured by ELISA |
| sPLA2 Levels in EBC during ACS versus Steady-State | Time point 1 to Time point 2 (at 2 week follow-up) | Comparison of sPLA2 levels in EBC from Time point 1 (during acute illness) and Time Point 2 (return to baseline status at 2 week follow up). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| sPLA2 levels in EBC versus Plasma | Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission)] | Difference in sPLA2 levels from EBC compared with Plasma during Time point 1 (during acute illness) |
Countries
United States
Outcome results
None listed