Exhaled Breath Particles as a Clinical Indicator for Lung Injury and Acute Respiratory Distress Syndrome (ARDS)

NCT ID: NCT04503057

Last Updated: 2022-04-12

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2025-05-01

Brief Summary

Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of coronavirus (COVID19). The investigators have recently shown that Exhaled Breath Particles (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive real-time early detection method for primary graft dysfunction (which bears a pathophysiological resemblance to ARDS) in lung transplant patients. The investigators have also previously demonstrated the utility of PFR in early detection and monitoring of ARDS in a large animal model. PFR has been shown to be elevated prior to the cytokine storm which classically occurs in ARDS. Early detection of ALI and ARDS is intimately linked to a patient's chance of survival as early treatment consisting of the preparation for intensive care, prone positioning and protective mechanical ventilation can be implemented early in the process. In the present study the investigators aim to use real-time PFR as an early detector for COVID19-induced ARDS. The investigators will also collect EBPs onto a membrane for subsequent molecular analysis. Previous studies have shown that most of those proteins found in bronchoalveolar lavage (BAL) can also be detected in EBPs deposited on membranes. The investigators therefore also aim to be able to diagnose COVID19 by analyzing EBPs using Polymerase Chain Reaction (PCR) with the same specificity as PCR from BAL, with the added benefit of being able to identify protein biomarkers for early detection of ARDS.

Detailed Description

EBP will be measured on 100 patients who are coronavirus (COVID-19) positive as indicated by PCR tests. Measurement will be done on daily basis from the time the patient is admitted to the hospital as an inpatient until either discharge or transition to ICU care. The initiation of mechanical ventilation in ICU patients will facilitate the tracking of EBP patterns over the course of disease in each patient. EBP measurements will also be done on 100 patients without COVID19 infection who have normal lung function as a control cohort.

The study will involve measurements on patients who have been placed on mechanical ventilation in the ICU. The purpose of utilizing PFR will be to reduce the need for invasive diagnostic tests such as bronchoscopy and for hospital transportation associated with tests such as CT scans. This will ultimately serve to not only decrease the risk of infecting other patients and staff in the hospital environment, but also to facilitate careful monitoring of these critical patients by measuring the extent of lung injury over time. In addition to PFR, EBP will be collected and measured on a daily basis to track the EBP patterns on patients in mechanical ventilation. Pre-clinical studies have shown that EBP can measure the extent of lung injury over time (onset of ARDS and recovery (unpublished data))

Measurements are also planned for patients who are on mechanical ventilation on extracorporeal membrane oxygenation (ECMO) support as well.

Conditions

Covid19; ARDS, Human; ALI

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

COVID-19 positive

COVID-19-positive patients with pulmonary infection, ALI or ARDS

No interventions assigned to this group

COVID-19 negative

COVID-19-negative patients with pulmonary infection, ALI or ARDS

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Clinical diagnosis of ALI
• Clinical diagnosis of ARDS
• COVID-19 infection as measured by a positive PCR test

Exclusion Criteria

• Dementia
• Severe neurological disease
• Drug abuse

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lund University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra Lindstedt Ingemansson, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Region Skåne, Lund University

Locations

Region Skåne

Lund, Skåne County, Sweden

Site Status: RECRUITING

Countries

Sweden

Central Contacts

Sandra Lindstedt Ingemansson, MD, PhD

Role: CONTACT

sandra.lindstedt_ingemansson@med.lu.se

+46737220580

Leif Pierre, PhD

Role: CONTACT

leif.pierre@skane.se

+467073096605

Facility Contacts

Sandra Lindstedt Ingemansson, MD, PhD

Role: primary

sandra.lindstedt_ingemansson@med.lu.se

0737220580

Leif Pierre, PhD

Role: backup

leif.pierre@skane.se

+46703096605

References

Broberg E, Andreasson J, Fakhro M, Olin AC, Wagner D, Hyllen S, Lindstedt S. Mechanically ventilated patients exhibit decreased particle flow in exhaled breath as compared to normal breathing patients. ERJ Open Res. 2020 Feb 10;6(1):00198-2019. doi: 10.1183/23120541.00198-2019. eCollection 2020 Jan.

Reference Type: BACKGROUND

PMID: 32055633 (View on PubMed)

Stenlo M, Hyllen S, Silva IAN, Bolukbas DA, Pierre L, Hallgren O, Wagner DE, Lindstedt S. Increased particle flow rate from airways precedes clinical signs of ARDS in a porcine model of LPS-induced acute lung injury. Am J Physiol Lung Cell Mol Physiol. 2020 Mar 1;318(3):L510-L517. doi: 10.1152/ajplung.00524.2019. Epub 2020 Jan 29.

Reference Type: BACKGROUND

PMID: 31994907 (View on PubMed)

Broberg E, Hyllen S, Algotsson L, Wagner DE, Lindstedt S. Particle Flow Profiles From the Airways Measured by PExA Differ in Lung Transplant Recipients Who Develop Primary Graft Dysfunction. Exp Clin Transplant. 2019 Dec;17(6):803-812. doi: 10.6002/ect.2019.0187. Epub 2019 Oct 11.

Reference Type: BACKGROUND

PMID: 31615381 (View on PubMed)

Other Identifiers

PEx ARDS

Identifier Type: -

Identifier Source: org_study_id