Neutrophil Phenotypic Profiling and Acute Lung Injury in Patients After Cardiopulmonary Bypass (CPB)

Cardiopulmonary Bypass Clinical Trial

Official title:

Neutrophil Phenotypic Profiling and Acute Lung Injury in Patients After Cardiopulmonary Bypass (CPB)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04296071
• Other study ID #: IRB-P00034280
• Status: Recruiting
• Start date: October 14, 2022
• Est. completion date: December 2024

Study information

• Verified date: September 2023
• Source: Boston Children's Hospital
• Contact: Sophia Koutsogiannaki, PhD
• Phone: 617-919-4725
• Email: sophia.koutsogiannaki[@]childrens.harvard.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Acute lung injury (ALI) following cardiopulmonary bypass (CPB) is a serious complication, often prolonging the length of stay in ICU and potentially dealing to mortality. The objective of this study is to assess the mechanism of CPB-mediated acute lung injury in pediatric patients.

Description:

Acute lung injury (ALI) is frequently associated with the use of extracorporeal circulation during cardiopulmonary bypass (CPB) surgery and develops postoperatively in 2-3% of cardiac surgical patients. Histological evidence shows that CPB increases pulmonary vascular permeability and extravascular lung water content while diminishing pulmonary compliance. Furthermore, some patients can develop acute respiratory distress syndrome, which has a mortality rate of 50-70%. Recruitment of intrapulmonary neutrophils is a characteristic of ALI following CPB. Blood contact with non-physiological surfaces, cooling and rewarming and mechanical shear stress activate neutrophils. The recruitment of activated neutrophils from blood vessels to local tissue involves a chain of well-coordinated events, including adhesion, tethering, rolling and crawling, followed by trans-endothelial and trans-epithelial migration. Activation of sequestered neutrophils causes the release of specific proteolytic enzymes and oxygen free radicals, which leads to increased alveolar-endothelial permeability and parenchymal damage. During CPB, the lungs are almost completely excluded from the systemic circulation, which causes the blood within them to be almost 'static'. Pulmonary tissue hypoxia and re-oxygenation combined with vascular ischemia and reperfusion induce the generation of chemokines, which contributes to subsequent injury by accumulating and entrapping activated neutrophils. The accumuled and entrapped activated neutrophils in the lungs and the subsequent release of toxic substances render the lungs highly susceptible to this damage. However, the mechanism that drives neutrophil migration to the lungs after CPB is not well studied. This study will delineate the mechanisms of neutrophil migration to the lung and subsequent lung injury after CPB.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: December 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 12 Months

Eligibility

Inclusion Criteria:

• Are < 12months of age

• Scheduled for cardiac surgical needing CPB

• Preoperative SpO2 > 90%

Exclusion Criteria:

• Lack of parental (or legal guardian's) consent

• Preoperative SpO2 < 90%

• Preoperative oxygen therapy

Related Conditions & MeSH terms

• Acute Lung Injury
• Cardiopulmonary Bypass
• Lung Injury
• Wounds and Injuries

Intervention

Other:
• Research study
Blood and tracheal aspirates will be collected

Locations

Country	Name	City	State
United States	Boston Children's Hospital	Boston	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Sophia Koutsogiannaki

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Perform neutrophil analysis in blood and tracheal aspirates samples	We will analyze neutrophil profiles in the blood and tracheal aspirates	2 years
Secondary	Determine chemoattractant levels	We will measure the levels of chemoattractants in the blood and tracheal aspirates	2 years
Secondary	Determine neutrophil functions	We will measure neutrophil functions from the blood and tracheal aspirates	2 years