Clinical trial NCT02201446: The Role of Circulating Soluble CD74 in Acute Lung Injury
Official title: Relationship Between Elevated Soluble Cluster of Differentiation 74 (CD74) and Severity of Experimental and Clinical ALI/ARDS.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Lung Injury
Acute Respiratory Distress Syndrome
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2014-07-28
Enrollment: 139
Sex: ALL
Minimum age (years): 16
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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.

Primary outcomes:
measure: Number of Participants Receiving Mechanical Ventilation
timeFrame: up to 28 days
measure: Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)
timeFrame: up to 28 days
measure: Acute Physiology and Chronic Health Evaluation (APACHE) II Scores
timeFrame: up to 28 days
measure: Serum Soluble Cluster of Differentiations 74 (sCD74)
timeFrame: Day 1
measure: Serum Soluble Cluster of Differentiations 74 (sCD74)
timeFrame: Day 3
Secondary outcomes:
measure: Length of Stay in the ICU
timeFrame: 1 year
measure: Length of Hospital Stay
timeFrame: 1 year
measure: Days of Unassisted Ventilation
timeFrame: 1 year
measure: Death
timeFrame: up to 28 days
measure: TNF-α
timeFrame: Day 3
measure: IL-6
timeFrame: Day 3
measure: MIF
timeFrame: Day 3
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Burn and Trauma Sugery, Changhai Hospital
Study officials:
affiliation: Department of Burn Sugery, Changhai Hospital
name: Zhaofan Xia, MD PhD
role: STUDY_DIRECTOR
References:
citation: 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.