The Role of Circulating Soluble CD74 in Acute Lung Injury

• ClinicalTrials.gov Identifier: NCT02201446
• Recruitment Status: Completed
• First Posted: July 28, 2014
• Results First Posted: December 15, 2016
• Last Update Posted: February 17, 2017
• Sponsor: Changhai Hospital
• Information provided by (Responsible Party): Zhaofan Xia, Changhai Hospital

Study Description

Brief Summary:

Efforts to identify circulating factors that predict severity of acute lung injury/acute respiratory distress syndrome（ALI/ARDS） patients is unrevealing. The primary purpose of this study is to verify our hypothesis that soluble CD74 might be a potential novel ALI/ARDS biomarker.

Condition or disease
Acute Lung Injury; Acute Respiratory Distress Syndrome

Detailed Description:

Acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) is a devastating cause of morbidity and mortality characterized by alveolar epithelial and endothelial injury. Despite recent advances in pathogenetic mechanisms and therapy strategies of ALI, efforts to identify circulating factors that predict severity of ALI/ARDS patients have been unrevealing.

CD74 (also known as a major histocompatibility complex (MHC) class II invariant chain) is a type II transmembrane protein, recently found to be the high-affinity receptor of macrophage migration inhibitory factor (MIF). MIF promotes neutrophil accumulation in alveolar space via binding to CD74 expressed on the cell surface. Our previous study， consistent with others, has shown that MIF was highly expressed in acute lung injury (ALI). In addition, we also detected highly CD74 expression in lipopolysaccharide (LPS)-induced ALI mouse model. Recently, a circulating form of CD74 was discovered in autoimmune liver disease. Similarly, we investigated the existence of soluble form of CD74 in serum and bronchoalveolar lavage fluid (BALF) in ALI mouse model and burn or trauma related ALI patients. Based on these finds, we postulated that soluble CD74 might participate in regulating lung inflammation and be a potential novel ALI/ARDS biomarker.

Study Design

• Study Type: Observational
• Actual Enrollment: 139 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Relationship Between Elevated Soluble Cluster of Differentiation 74 (CD74) and Severity of Experimental and Clinical ALI/ARDS.
• Study Start Date: March 2014
• Actual Primary Completion Date: November 2014
• Actual Study Completion Date: April 2015

Groups and Cohorts

Group/Cohort
ARDS patients; Eighty-one patients were enrolled consecutively over a two-year time period (2014-2015) and identified as ARDS prospectively according to the Berlin definitions of the European Society of Intensive Care Medicine and American Thoracic Society on ARDS. Exclusion criteria were an age of less than 16 years, pregnancy, chronic obstructive pulmonary disease according to medical history and failure to obtain informed consent.
Healthy volunteers; Fifty-eight healthy volunteers recruited from the general population who had no significant medical history and no medications were categorized as control patients.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Receiving Mechanical Ventilation [ Time Frame: up to 28 days ]
2. Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2) [ Time Frame: up to 28 days ]
3. Acute Physiology and Chronic Health Evaluation (APACHE) II Scores [ Time Frame: up to 28 days ]
   APACHE II scores range from 0 to 71. A higher values represent a worse outcome.
4. Serum Soluble Cluster of Differentiations 74 (sCD74) [ Time Frame: Day 1 ]
   The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.
5. Serum Soluble Cluster of Differentiations 74 (sCD74) [ Time Frame: Day 3 ]
   The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.

Secondary Outcome Measures :

1. Length of Stay in the ICU [ Time Frame: 1 year ]
2. Length of Hospital Stay [ Time Frame: 1 year ]
3. Days of Unassisted Ventilation [ Time Frame: 1 year ]
4. Death [ Time Frame: up to 28 days ]
5. TNF-α [ Time Frame: Day 3 ]
6. IL-6 [ Time Frame: Day 3 ]
7. MIF [ Time Frame: Day 3 ]

Biospecimen Retention:   Samples Without DNA

ARDS patients and healthy volunteers

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 100 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Patients with and without ARDS were screened from Changhai Hospital. Patients were enrolled consecutively over a 2-year time period (2014-2015). All enrolled patients with ALI met the American-European Consensus Committee criteria.In addition, healthy individuals were recruited from the general population.

Criteria

Inclusion Criteria:

• Clinical diagnosis of ALI/ARDS
• Informed consent was obtained from either the subjects themselves or from designated surrogates before enrollment in the study.

Exclusion Criteria:

• Patients who have chronic lung disease before enrollment.
• Patients who have severe organ dysfunction, autoimmune diseases and tumor.
• Women who are pregnant or breast-feeding.
• Patients who, in the opinion of the Investigator, have any other medical condition which renders the patient unable to complete the study or which would interfere with optimal participation in the study or produce significant risk to the patient.
• Patients participating in or planning to enroll in another clinical trial during the time of the study.

Contacts and Locations

Locations

China

Department of Burn and Trauma Sugery, Changhai Hospital

Shanghai, China, 200433

Sponsors and Collaborators

Changhai Hospital

Investigators

• Study Director: Zhaofan Xia, MD PhD; Department of Burn Sugery, Changhai Hospital

More Information

Publications of Results:

Wu G, Sun Y, Wang K, Chen Z, Wang X, Chang F, Li T, Feng P, Xia Z. Relationship between elevated soluble CD74 and severity of experimental and clinical ALI/ARDS. Sci Rep. 2016 Jul 22;6:30067. doi: 10.1038/srep30067.

• Responsible Party: Zhaofan Xia, President, Changhai Hospital
• ClinicalTrials.gov Identifier: NCT02201446
• Other Study ID Numbers: 20131224
• First Posted: July 28, 2014
• Results First Posted: December 15, 2016
• Last Update Posted: February 17, 2017
• Last Verified: January 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Wounds and Injuries; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Thoracic Injuries