Avalanche Phenomenon During Airways Opening in Acute Respiratory Distress Syndrome (AVALANCHE)

Acute respiratory distress syndrome accounts for 23% of mechanically ventilated patients and is associated with high mortality rate. Although life-saving, mechanical ventilation may worsen lung injury through two main mechanisms: lung overdistension and atelectrauma. Indeed, the cyclic opening and closure of airways during tidal ventilation may cause lung and bronchial injuries as suggested by animal models and autopsy findings. Complete airways closure has recently been described in 40% of patients with acute respiratory distress syndrome, and setting positive end-expiratory pressure above the airway opening pressure may limit atelectrauma. However, animal and mathematical models suggest that above the airway opening pressure, more distal airways open unevenly according to their own opening pressure, resulting in an "avalanche"-like phenomenon during lung inflation. This phenomenon has never been described in humans. A better understanding of the opening of airways in acute respiratory distress syndrome may help to limit ventilation-induced lung injury and to improve outcomes.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Other: Airway pressure, flow, esophageal pressure, ventilation distribution

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Rémi Coudroy, MD, PhD; Phone Number: + 33 5 49 44 40 07; Email: remi.coudroy@chu-poitiers.fr
• Study Contact Backup: Name: Céline DELETAGE; Phone Number: +33 5 49 44 38 54; Email: celine.deletage@chu-poitiers.fr

Study Locations

• France
  • Poitiers, France, 86000
    • Recruiting
    • CHU Poitiers
    • Contact: Rémi COUDROY, Pr; Email: remi.coudroy@chu-poitiers.fr

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with moderate-to-severe acute respiratory distress syndrome will be included within the first 72 hours after meeting the Berlin definition criteria.

After ruling out exclusion criteria and obtaining informed consent from their relatives, patients will be included in the study.

Description

Inclusion Criteria:

• Age ≥ 18
• Moderate-to-severe acute respiratory distress syndrome within the first 72 hours after meeting the Berlin definition criteria:
• Within 1 week of a known clinical insult or new or worsening respiratory symptoms;
• Bilateral opacities (not fully explained by effusions, lobar/lung collapse, or nodules);
• Respiratory failure not fully explained by cardiac failure or fluid overload;
• PaO2/FiO2 ≤ 200 mmHg with positive end-expiratory pressure ≥ 5 cmH2O.
• Absence of spontaneous breathing efforts
• Consent to participate to the study from the patient and/or its surrogate

Exclusion Criteria:

• Pneumothorax
• Broncho-pleural fistula
• Tracheostomy
• Hemodynamic instability
• Severe hypoxemia
• Suspected of proven intracranial hypertension
• Chronic obstructive lung disease
• Pacemaker or defibrillator
• Decision to withhold of withdraw life-sustaining measures
• Under protection

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the prevalence of "avalanche" phenomenon during low-flow lung inflation.	The distribution of pressure drops on low-flow inflation pressure-volume curves will be described and plotted on a log-log scale graph. "Avalanche" phenomenon will be defined if this distribution follows power law (i.e. is linear on a log-log scale) with a R2 ≥ 0.80. The prevalence of "avalanche" phenomenon will be described as frequency and 95% confidence interval.	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare characteristics of patients and their outcomes according to the existence of "avalanche" phenomenon during low-flow lung inflation.	Continuous variables will be summarized as mean ± standard deviation or median [25th-75th percentile] according to their distribution and compared by means of the Mann-Whitney or the Student's t test. Categorical variables will be summarized as frequency (percentage) and 95% confidence interval, and compared by means of Fisher or Chi2 test.	Day 28
To assess the existence of an inflection point on the low-flow deflation pressure-volume curve.	The slope of the low-flow deflation pressure-volume curve will be computed by means of linear regression and summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution. The existence of an inflexion point will be summarized as number (percentage) and 95% confidence interval. The airway pressure corresponding to this inflexion point will be summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution.	At inclusion
To assess the airway pressure value of the inflection point on the low-flow deflation pressure-volume curve in patients with an inflexion point on the low-flow deflation pressure-volume curve	The airway pressure corresponding to the inflexion point on the low-flow deflation pressure-volume curve will be summarized as mean ± standard deviation or median [25th-75th percentile] according to its distribution.	At inclusion

Collaborators and Investigators

• Sponsor: Poitiers University Hospital

Publications and helpful links

General Publications

• Chen L, Del Sorbo L, Grieco DL, Shklar O, Junhasavasdikul D, Telias I, Fan E, Brochard L. Airway Closure in Acute Respiratory Distress Syndrome: An Underestimated and Misinterpreted Phenomenon. Am J Respir Crit Care Med. 2018 Jan 1;197(1):132-136. doi: 10.1164/rccm.201702-0388LE. No abstract available.
• Suki B, Barabasi AL, Hantos Z, Petak F, Stanley HE. Avalanches and power-law behaviour in lung inflation. Nature. 1994 Apr 14;368(6472):615-8. doi: 10.1038/368615a0.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): December 24, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Respiratory Distress Syndrome
• Other Study ID Numbers: AVALANCHE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No