Clinical trial NCT03250585: sPLA2 in EBC During Acute Chest Syndrome
Official title: Secretory Phospholipases A2 in Exhaled Breath Condensate From Sickle Cell Patients With Acute Chest Syndrome: A Feasibility Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Sickle Cell Disease
Acute Chest Syndrome
Keywords: acute chest syndrome
secretory phospholipases A2
exhaled breath condensate
sickle cell disease
Lead sponsor: Virginia Commonwealth University
Sponsor class: OTHER
First posted: 2017-08-15
Enrollment: 6
Sex: ALL
Minimum age (years): 7
Maximum age (years): 30
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Sickle cell patients with acute chest syndrome

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.

Eligibility criteria: 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)

Primary outcomes:
measure: sPLA2 Measurement in EBC during ACS
timeFrame: Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission)
measure: sPLA2 Levels in EBC during ACS versus Steady-State
timeFrame: Time point 1 to Time point 2 (at 2 week follow-up)
Secondary outcomes:
measure: sPLA2 levels in EBC versus Plasma
timeFrame: Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission)]
Other outcomes:
Locations:
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Virginia Commonwealth University
name: Davis D Michael, PhD
role: PRINCIPAL_INVESTIGATOR
References: