Laboratory Biomarkers and Pulmonary Interstitial Emphysema in ARDS (PIE-ARDS)

NCT06001645 | Recruiting

• 1 other identifier: PNRR-MAD-2022-12376
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 4

Brief Summary

Barotrauma (pneumothorax, pneumomediastinum) is a well-described complication of Acute Respiratory Distress Syndrome (ARDS), especially in patients with coronavirus disease 2019 (COVID-19) (16.1% in COVID-19, and about 6% in non-COVID-19 ARDS). Macklin effect was recently discovered by our group as an accurate radiological predictor of barotrauma in COVID-19 ARDS; the Investigators also found that density histograms automatically extracted from chest CT images provide a reliable insight into lung composition . Since lung frailty is a major issue also in non-COVID-19 ARDS, the Investigators want to confirm the predictive role of Macklin effect also in this setting. In addition, the Investigators aim to explore inflammatory profiling to decipher different biological aspects of the same clinical issue. Finally, the Investigators want to develop a specific management algorithm for patients diagnosed, according to our findings, with a specific ARDS sub phenotype characterized by increased lung frailty

Conditions

Acute Respiratory Distress Syndrome; Barotrauma

Keywords

Acute Respiratory Distress Syndrome; Mechanical Ventilation; Intensive Care; Respiratory Failure; Pneumothorax; Macklin effect

Outcome Measures

Primary Outcomes (1)

• Rate of clinically relevant barotrauma

  Barotrauma is diagnosed only in the case of clear radiological evidence (free air at chest X-ray and/or chest CT scan). Rate of barotrauma will be compared between patients with an hyperinflammatory pattern as compared with control.

  30 days or until hospital discharge. Specifically, from date of basal CT scan until the date of first radiologically documented barotrauma

Study Arms (1)

Acute Respiratory Distress Syndrome

Patients with ARDS requiring or not requiring invasive ventilation

Diagnostic Test: Blood and bronchoalveolar fluid collection and analysis; Diagnostic Test: Chest CT scan

Interventions

Blood and bronchoalveolar fluid collection and analysis DIAGNOSTIC_TEST

Blood and bronchoalveolar lavage fluid will be collected within 12 hours after intubation. Blood samples will be centrifuged, and the serum immediately stored at less than 70° C. The following biomarkers will be analysed in the serum and bronchoalveolar lavage fluid: Interleukin-8 (IL-8), Interleukin (IL)-6, IL-1Ra, IL-18, interferon (IFN ), Angiopoietin-2 (Ang-2), Tumour Necrosis Factor receptor-1 (TNFr1), Plasminogen Activator Inhibitor-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, and metalloproteases (MMP9, MMP10). Blood samples obtained from the patients will be placed in specimen tubes containing heparin, centrifuged at 1500 G for 10 minutes, and then the plasma will be aspirated and stored at -70° C. Bronchoalveolar lavage fluid will be centrifuged at 1500 G for 10 minutes to remove cellular contents and stored at -70° C.

Acute Respiratory Distress Syndrome

Chest CT scan DIAGNOSTIC_TEST

Computed Tomography Scan per normal clinical practice

Acute Respiratory Distress Syndrome

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with ARDS diagnosis will be enrolled. With the exception of blood and BAL samples collection, all patients enrolled in the prospective cohort will follow their normal course of diagnosis/treatment without any further requirements for the scope of this study other than those provided in the normal management of patients with this condition. Furthermore, any decision regarding drug or procedure will be made by the physician based on her/his clinical judgment, independently from the decision to include the patient in this study. No follow-up medical and/or imaging examinations/laboratory analysis after hospital discharge are needed by the present study design.

You may qualify if:

• Clinical and radiological signs of ARDS, according to Berlin criteria, requiring ICU admission;
• Obtain duly signed informed consent
• Availability of at least one chest CT scan during hospital stay

You may not qualify if:

• Poor quality imaging (because of motion/respiratory artefacts).

Sponsors & Collaborators

• Università Vita-Salute San Raffaele: lead

Study Sites (4)

A.O.U. di Cagliari

Cagliari, Italy

NOT YET RECRUITING

IRCCS San Raffaele Scientific Institute

Milan, 20132, Italy

RECRUITING

A.O.U. Pisana

Pisa, Italy

NOT YET RECRUITING

Ospedale San Carlo

Potenza, Italy

NOT YET RECRUITING

Related Publications (7)

• Murayama S, Gibo S. Spontaneous pneumomediastinum and Macklin effect: Overview and appearance on computed tomography. World J Radiol. 2014 Nov 28;6(11):850-4. doi: 10.4329/wjr.v6.i11.850.

  PMID: 25431639 BACKGROUND

• Palumbo D, Zangrillo A, Belletti A, Guazzarotti G, Calvi MR, Guzzo F, Pennella R, Monti G, Gritti C, Marmiere M, Rocchi M, Colombo S, Valsecchi D, Scandroglio AM, Dagna L, Rovere-Querini P, Tresoldi M, Landoni G, De Cobelli F; COVID-BioB Study Group. A radiological predictor for pneumomediastinum/pneumothorax in COVID-19 ARDS patients. J Crit Care. 2021 Dec;66:14-19. doi: 10.1016/j.jcrc.2021.07.022. Epub 2021 Aug 12.

  PMID: 34392131 BACKGROUND

• Belletti A, Pallanch O, Bonizzoni MA, Guidi L, De Cobelli F, Landoni G, Zangrillo A, De Bonis M, Palumbo D. Clinical use of Macklin-like radiological sign (Macklin effect): A systematic review. Respir Med. 2023 Apr-May;210:107178. doi: 10.1016/j.rmed.2023.107178. Epub 2023 Feb 28.

  PMID: 36863617 BACKGROUND

• Paternoster G, Bertini P, Belletti A, Landoni G, Gallotta S, Palumbo D, Isirdi A, Guarracino F. Venovenous Extracorporeal Membrane Oxygenation in Awake Non-Intubated Patients With COVID-19 ARDS at High Risk for Barotrauma. J Cardiothorac Vasc Anesth. 2022 Aug;36(8 Pt B):2975-2982. doi: 10.1053/j.jvca.2022.03.011. Epub 2022 Mar 17.

  PMID: 35537972 BACKGROUND

• Maccarrone V, Liou C, D'souza B, Salvatore MM, Leb J, Belletti A, Palumbo D, Landoni G, Capaccione KM. The Macklin effect closely correlates with pneumomediastinum in acutely ill intubated patients with COVID-19 infection. Clin Imaging. 2023 May;97:50-54. doi: 10.1016/j.clinimag.2023.03.003. Epub 2023 Mar 4.

  PMID: 36889115 BACKGROUND

• Guarracino F, Baldassarri R, Brizzi G, Isirdi A, Landoni G, Marmiere M, Belletti A. Awake Venovenous Extracorporeal Membrane Oxygenation in the Intensive Care Unit: Challenges and Emerging Concepts. J Cardiothorac Vasc Anesth. 2025 Apr;39(4):1004-1014. doi: 10.1053/j.jvca.2024.12.045. Epub 2025 Jan 9.

  PMID: 39843275 BACKGROUND

• Belletti A, D'Andria Ursoleo J, Piazza E, Mongardini E, Paternoster G, Guarracino F, Palumbo D, Monti G, Marmiere M, Calabro MG, Landoni G, Zangrillo A. Extracorporeal membrane oxygenation for prevention of barotrauma in patients with respiratory failure: A scoping review. Artif Organs. 2025 Feb;49(2):183-195. doi: 10.1111/aor.14864. Epub 2024 Sep 21.

  PMID: 39305092 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood and bronchoalveolar lavage fluid will be collected within 12 hours after intubation; blood samples will be centrifuged, and the serum immediately stored at less than 70° C. The following biomarkers will be analysed in the serum and bronchoalveolar lavage fluid: Interleukin-8 (IL-8), Interleukin (IL)-6, IL-1Ra, IL-18, interferon (IFN ), Angiopoietin-2 (Ang-2), Tumour Necrosis Factor receptor-1 (TNFr1), Plasminogen Activator Inhibitor-1(PAI-1), Receptor for Advanced Glycation Endproducts (RAGE), Intercellular adhesion molecule-1 (ICAM-1), Surfactant Protein D (SPD), protein C, Von Willebrand Factor (VWF), CXCL10/CXCR3, and metalloproteases (MMP9, MMP10). Blood and BAL samples obtained from the patients will be placed in specimen tubes (containing heparin for plasma), centrifuged at 1500 G for 10 minutes, and then stored at -70° C

MeSH Terms

Conditions

Respiratory Distress Syndrome; Barotrauma; Respiratory Insufficiency; Pneumothorax

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Wounds and Injuries; Pleural Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: July 31, 2023
• First Posted: August 21, 2023
• Study Start: November 27, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)