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

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.

Study Overview

• Status: Recruiting
• Conditions: Lung Injury; Cardiopulmonary Bypass
• Intervention / Treatment: Other: Research study

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 56

Contacts and Locations

• Study Contact: Name: Sophia Koutsogiannaki, PhD; Phone Number: 617-919-4725; Email: sophia.koutsogiannaki@childrens.harvard.edu
• Study Contact Backup: Name: Koichi Yuki, MD; Phone Number: 617-355-6225; Email: koichi.yuki@childrens.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Rachel Bernier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 year (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

We will enroll patients < 12 months of age who undergo CPB surgery. This patient population is associated with the highest incidence of morbidity and mortality following cardiac surgery, due to often prolonged period of CPB. Patients will be categorized into two groups: Group 1: patients who tend to have longer CPB (> 3 h), (ASO, Stage 1, IAA repair, Truncus repair, TAPVR) and Group 2: Patients who have shorter CPB (< 3hrs VSD, TOF, ASD).

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; patients who tend to have longer CPB	Other: Research study; Blood and tracheal aspirates will be collected
Group 2; Patients who have shorter CPB	Other: Research study; Blood and tracheal aspirates will be collected

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perform neutrophil analysis in blood and tracheal aspirates samples	We will analyze neutrophil profiles in the blood and tracheal aspirates	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine chemoattractant levels	We will measure the levels of chemoattractants in the blood and tracheal aspirates	2 years
Determine neutrophil functions	We will measure neutrophil functions from the blood and tracheal aspirates	2 years

Collaborators and Investigators

• Sponsor: Sophia Koutsogiannaki

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 3, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Respiratory Tract Diseases; Lung Diseases; Thoracic Injuries; Lung Injury
• Other Study ID Numbers: IRB-P00034280

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No