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

• ClinicalTrials.gov Identifier: NCT04503057
• Recruitment Status: Recruiting
• First Posted: August 6, 2020
• Last Update Posted: April 12, 2022
• Sponsor: Lund University Hospital
• Information provided by (Responsible Party): Lund University Hospital

Tracking Information

• First Submitted Date: August 3, 2020
• First Posted Date: August 6, 2020
• Last Update Posted Date: April 12, 2022
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 4, 2022)

• Concentration of COVID-19 through PCR testing of EBPs [ Time Frame: 12-36 months ]
  Real Time-PCR will be used to detect the presence of COVID-19 on membranes on which EBP have been collected to determine the efficacy of using the collection device for non-invasive detection of infection.
• Protein concentration in EBP [ Time Frame: 12-36 months ]
  Proteins will be measured in the samples of EBPs collected on the membrane for the purpose of identifying protein biomarkers of disease.
• Particle flow rate (particles per minute) in exhaled air [ Time Frame: 12-36 months ]
  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 (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR has been shown to increase before the cytokine storm which is a hallmark of ARDS. Early detection of ALI and ARDS is crucial for increasing a patient's chance of survival as it allows for early treatment, such as preparing for intensive care, prone positioning and protective mechanical ventilation settings. In the present study the investigators aim to use real-time PFR as an early detector for COVID-19-induced ARDS.

Original Primary Outcome Measures (submitted: August 5, 2020)

• COVID-19 RT-PCR detection in EBP [ Time Frame: 12-36 months ]
  Detect COVID-19 in EBP using RT-PCR
• Detection of proteins biomarkers in EBP [ Time Frame: 12-36 months ]
  Detection of proteins biomarkers in EBP
• Particle flow rate as an early indicator for lung injury [ Time Frame: 12-36 months ]
  We have recently shown that Exhaled Breath Particles (EBP) measured as particle flowrate (PFR) from the airways could be used as a noninvasive real time early detection method for primary graft dysfunction (similar to ARDS) in lung transplant patients and for ARDS in a large animal model. PFR increased before the cytokine storm. Early detection of ALI and ARDS is crucial for the patient's chance of survival as early treatment, such as preparing for intensive care, prone position and protective ventilation when the patient is treated in mechanical ventilation, can be implemented early in the process. In the present study we aim to use real time PFR as an early detector for COVID19 induced ARDS.

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Exhaled Breath Particles as a Clinical Indicator for Lung Injury and Acute Respiratory Distress Syndrome (ARDS)
• Official Title: Exhaled Breath Particles as a Clinical Indicator for Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) in Coronavirus (Covid-19) Positive and Negative Patients
• 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.

• Study Type: Observational [Patient Registry]
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: 12 Months

Biospecimen

Retention:   Samples With DNA

Description:

Blood samples, broncho alveolar lavage sample, exhaled breath particles

• Sampling Method: Probability Sample
• Study Population: Patients with pulmonary infection, ALI or ARDS. Patients on mechanical ventilation. Normal breathing patients. Patients on ECMO support.

Condition

• Covid19
• ARDS, Human
• ALI

• Intervention: Not Provided

Study Groups/Cohorts

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

Publications *

• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 5, 2020): 300
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 1, 2025
• Estimated Primary Completion Date: May 1, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 90 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sandra Lindstedt Ingemansson, MD, PhD; +46737220580; sandra.lindstedt_ingemansson@med.lu.se

Contact: Leif Pierre, PhD; +467073096605; leif.pierre@skane.se

• Listed Location Countries: Sweden

Administrative Information

• NCT Number: NCT04503057
• Other Study ID Numbers: PEx ARDS
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Lund University Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Lund University Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Sandra Lindstedt Ingemansson, MD, PhD; Region Skåne, Lund University

• PRS Account: Lund University Hospital
• Verification Date: January 2022