Understanding the Role of Genes and Biomarkers in the Blood Clotting Process in Children With Acute Lung Injury

ALI/ARDS is a life-threatening condition that involves inflammation of the lungs and fluid
accumulation in the air sacs, which leads to low blood oxygen levels and respiratory
failure. Common causes include pneumonia, sepsis, and lung trauma. Symptoms, including
breathing difficulty, low blood pressure, and organ failure, usually develop within 24 to 48
hours of the original injury or illness. Most patients require immediate care in an
intensive care unit, and the main form of treatment is mechanical ventilation, which
delivers oxygen and a continuous level of pressure to the damaged lungs. Although progress
has been made in understanding how ALI/ARDS develops, it is still unknown why recovery
outcomes differ among people. Differences in the genetic basis of protein C and fibrinolysis
pathways, which both play a role in preventing blood clots, may be a factor in determining
the severity of and recovery from ALI. The purpose of this study is to analyze plasma and
DNA from children with ALI/ARDS to identify biomarkers and genetic variations that may be
related to clinical outcomes.

This study will enroll children who are hospitalized with ALI/ARDS. Participants' medical
records will be reviewed to gather information about symptoms, physical exam findings,
mechanical ventilator settings, and laboratory test results. A blood collection will occur
on Days 1 and 3. Study researchers will analyze plasma biomarkers and use high throughput
DNA sequencing technology to analyze participants' DNA.

Inclusion Criteria:

- Hospitalized and requiring supplemental oxygen

- Meets the American-European consensus definition of ALI/ARDS, defined as partial
pressure of oxygen in arterial blood/fraction of inspired oxygen (PaO2/FiO2) ratio of
less than 300 mm Hg, bilateral opacities on a chest radiograph, and either a
pulmonary wedge pressure of less than 18 mm Hg or the absence of clinical evidence of
left atrial hypertension

- Acute pulmonary parenchymal disease (i.e., onset of bilateral infiltrates on chest
radiograph within 48 hours of screening)

- PaO2/FiO2 less than or equal to 300 mm Hg, regardless of the mean airway pressure

- At least one arterial blood gas confirming partial pressure of oxygen/fraction of
inspired oxygen (PO2/FiO2) ratio less than 300 mm Hg or Fi02/Sao2 on pulse oximetry
of less than 320

Exclusion Criteria:

- Clinical signs of left ventricular failure, pulmonary capillary wedge pressure
greater than 18 mm Hg, or evidence, such as echocardiography, suggesting a cardiac
basis for the pulmonary edema

- Presence of right-to-left intracardiac shunt