Neutrophil Elastase and Elafin as Prognostic Biomarker for Acute Respiratory Distress Syndrome

The acute respiratory distress syndrome (ARDS), characterized by alveolar flooding with protein-rich pulmonary edema fluid, is one of the most common disease in the intensive care unit (ICU) throughout the world. In recent years, much effort has been focused on the biological markers for their potential values to diagnose ARDS and outcomes.

ARDS is generally accompanied by the disruption in alveolar-capillary barrier permeability, which subsequently caused an influx of neutrophils into the interstitium and alveolar space. It was reported that the aggregation, adhesion activation and release proteases of neutrophils are the key pathogenesis of ARDS pulmonary edema. Neutrophil Elastase (HNE), the most crucial protease generated in neutrophil azurophilic granules, plays an important role in various inflammations, especially the lung injury. The destructive action of HNE on almost all extracellular matrix influences cell signaling through cleavage of surface receptors. Once released in circulation, HNE is rapidly inactivated by conjugation with PI3. This local inhibitor reduces HNE mediated tissue injury and inflammation. Thus, the investigators plan to conduct a cohort study with repeated measures to examine the diagnostic and prognostic value of HNE and PI3 for ARDS.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome, ARDS

• Study Type: Observational
• Enrollment (Actual): 500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Study population is from five clinical and surgical ICUs in Beijing metropolitan area: Peking University Third Hospital in the northwest of Beijing, Beijing Friendship Hospital in the south, Beijing Shijitan Hospital in the middle, Beijing Xiyuan Hospital in the west, and China-Japan Friendship Hospital in the northeast.

Description

Exclusion Criteria:

• Age <18 years
• History of chronic lung diseases, such as interstitial pulmonary fibrosis or bronchiolitis
• history of pneumonectomy
• Treatment with immunomodulating therapy other than corticosteroids, such as granulocyte colony stimulating factor, cyclophosphamide, cyclosporine, interferon, or TNF-α antagonists
• Presence of other immunodeficient conditions, such as HIV infection, leukemia, or neutropenia (absolute neutrophil count <1000/μl)
• History of organs or bone marrow transplant other than autologous bone marrow transplant
• Directive to withhold intubation
• ICU stay duration<72h
• Patient developed ARDS before ICU admission. Sepsis and septic shock were defined according to the Berlin definition

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort
Peking University Third Hospital
Beijing Friendship Hospital
Beijing Shijitan Hospital
Beijing Xiyuan Hospital
China-Japan Friendship Hospital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ARDS development-Berlin definition	60 days
ARDS survival	60 days

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Beijing Friendship Hospital; Beijing Shijitan Hospital, Capital Medical University; China-Japan Friendship Hospital; Beijing Xiyuan Hospital

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: October 21, 2016
• First Submitted That Met QC Criteria: October 23, 2016
• First Posted (Estimate): October 25, 2016

Study Record Updates

• Last Update Posted (Estimate): October 25, 2016
• Last Update Submitted That Met QC Criteria: October 23, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 2009-1014

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