Acute Lung Injury, Acute Respiratory Distress Syndrome
Conditions
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.
Interventions
None listed
Sponsors
Changhai Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
16 Years to 100 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Receiving Mechanical Ventilation | up to 28 days | — |
| Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2) | up to 28 days | — |
| Acute Physiology and Chronic Health Evaluation (APACHE) II Scores | up to 28 days | APACHE II scores range from 0 to 71. A higher values represent a worse outcome. |
| Serum Soluble Cluster of Differentiations 74 (sCD74) | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Days of Unassisted Ventilation | 1 year |
| IL-6 | Day 3 |
| TNF-α | Day 3 |
| Death | up to 28 days |
| MIF | Day 3 |
| Length of Stay in the ICU | 1 year |
| Length of Hospital Stay | 1 year |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 81 |
| 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. | 58 |
| Total | 139 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Total | ARDS Patients |
|---|---|---|---|
| Age, Continuous | 39.52 years STANDARD_DEVIATION 10.43 | 44.47 years STANDARD_DEVIATION 14.58 | 48.02 years STANDARD_DEVIATION 16.05 |
| Blood diseases | 0 participants | 0 participants | 0 participants |
| Day1 interleukin-6 (IL-6) | NA pg/ml | 101.63 pg/ml | 101.63 pg/ml |
| Day1 migration inhibitory factor (MIF) | NA ng/ml | 73.64 ng/ml STANDARD_DEVIATION 23.27 | 73.64 ng/ml STANDARD_DEVIATION 23.27 |
| Day1 tumor necrosis factor-α(TNF-α) | NA pg/ml | 97.09 pg/ml | 97.09 pg/ml |
| Diabetes mellitus | 0 participants | 8 participants | 8 participants |
| Gender Female | 26 Participants | 63 Participants | 37 Participants |
| Gender Male | 32 Participants | 76 Participants | 44 Participants |
| Hypertension | 0 participants | 15 participants | 15 participants |
| Inhalation injury | 0 participants | 46 participants | 46 participants |
| Kidney disease | 0 participants | 2 participants | 2 participants |
| Respiratory disease | 0 participants | 2 participants | 2 participants |
| Sequential Organ Failure Assessment(SOFA) | NA Scores on a scale | 7.16 Scores on a scale STANDARD_DEVIATION 3.7 | 7.16 Scores on a scale STANDARD_DEVIATION 3.7 |
| Trauma | 0 participants | 35 participants | 35 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 81 | 0 / 58 |
| serious Total, serious adverse events | 14 / 81 | 0 / 58 |
Outcome results
Primary
Acute Physiology and Chronic Health Evaluation (APACHE) II Scores
APACHE II scores range from 0 to 71. A higher values represent a worse outcome.
Time frame: up to 28 days
Population: not collected for healthy volunteers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | Acute Physiology and Chronic Health Evaluation (APACHE) II Scores | 14.35 Scores on a scale | Standard Deviation 6.39 |
| Healthy Volunteers | Acute Physiology and Chronic Health Evaluation (APACHE) II Scores | NA Scores on a scale | — |
Primary
Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2)
Time frame: up to 28 days
Population: not collected for healthy volunteers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2) | 2.1 ratio | Standard Deviation 0.46 |
| Healthy Volunteers | Fraction of Inspired Oxygen (FiO2)/Partial Arterial Oxygen Pressure (PO2) | NA ratio | — |
Primary
Number of Participants Receiving Mechanical Ventilation
Time frame: up to 28 days
Population: not collected for healthy volunteers
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARDS Patients | Number of Participants Receiving Mechanical Ventilation | 51 participants |
| Healthy Volunteers | Number of Participants Receiving Mechanical Ventilation | NA participants |
Primary
Serum Soluble Cluster of Differentiations 74 (sCD74)
The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | Serum Soluble Cluster of Differentiations 74 (sCD74) | 87.04 ng/ml | Standard Deviation 31.53 |
| Healthy Volunteers | Serum Soluble Cluster of Differentiations 74 (sCD74) | -14.77 ng/ml | Standard Deviation 15.57 |
Primary
Serum Soluble Cluster of Differentiations 74 (sCD74)
The concentration of sCD74 was determined using Elx800 (BioTek Instruments, Inc. VT), and normalization was based on concentration-response curves, using CD74 recombinant protein.
Time frame: Day 3
Population: Only 62 ARDS patients with Day 3 blood samples were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | Serum Soluble Cluster of Differentiations 74 (sCD74) | 132.92 ng/ml | Standard Deviation 40.4 |
| Healthy Volunteers | Serum Soluble Cluster of Differentiations 74 (sCD74) | -14.78 ng/ml | Standard Deviation 15.57 |
Secondary
Days of Unassisted Ventilation
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARDS Patients | Days of Unassisted Ventilation | 22 days |
| Healthy Volunteers | Days of Unassisted Ventilation | NA days |
Secondary
Death
Time frame: up to 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARDS Patients | Death | 14 participants |
| Healthy Volunteers | Death | 0 participants |
Secondary
IL-6
Time frame: Day 3
Population: Only 62 ARDS patients with Day 3 blood samples were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | IL-6 | 305.36 pg/ml | Standard Deviation 177.14 |
| Healthy Volunteers | IL-6 | NA pg/ml | — |
Secondary
Length of Hospital Stay
Time frame: 1 year
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARDS Patients | Length of Hospital Stay | 36.94 days |
| Healthy Volunteers | Length of Hospital Stay | NA days |
Secondary
Length of Stay in the ICU
Time frame: 1 year
Population: not collected for healthy volunteers
| Arm | Measure | Value (MEAN) |
|---|---|---|
| ARDS Patients | Length of Stay in the ICU | 23 days |
| Healthy Volunteers | Length of Stay in the ICU | NA days |
Secondary
MIF
Time frame: Day 3
Population: Only 62 ARDS patients with Day 3 blood samples were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | MIF | 129.27 ng/ml | Standard Deviation 41.12 |
| Healthy Volunteers | MIF | NA ng/ml | — |
Secondary
TNF-α
Time frame: Day 3
Population: Only 62 ARDS patients with Day 3 blood samples were analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ARDS Patients | TNF-α | 138.67 pg/ml | Standard Deviation 64.26 |
| Healthy Volunteers | TNF-α | NA pg/ml | — |