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

Targeted Genomic Analysis of Coagulation Pathways in Acute Lung Injury

Acute lung injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition that causes respiratory failure. This study will examine if differences in genes and biomarkers involved in the inflammation and blood clotting process may affect the severity of and recovery from ALI/ARDS in children hospitalized with the condition.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Adult

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 396

Contacts and Locations

Study Locations

• United States
  • California
    • Fresno, California, United States, 93710
      • Children's Hospital Central California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center of Oakland
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • American Family Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who are admitted to the University of California, San Francisco hospital and participating sites including Children's Hospital of Oakland with ALI/ARDS.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of ventilator-free days	Measured during participant's hospital stay

Secondary Outcome Measures

Outcome Measure	Time Frame
Mortality and organ dysfunction	Measured during participant's hospital stay

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Anil Sapru, MD, MAS, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Primary Completion (Actual): December 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 18, 2008
• First Submitted That Met QC Criteria: January 18, 2008
• First Posted (Estimate): January 31, 2008

Study Record Updates

• Last Update Posted (Actual): July 20, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Acute Respiratory Distress Syndrome; Acute Lung Injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Wounds and Injuries; Infant, Newborn, Diseases; Infant, Premature, Diseases; Thoracic Injuries; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury
• Other Study ID Numbers: 545; K23HL085526 (U.S. NIH Grant/Contract); K23HL085526-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No