Role of Dyspnea in the Progression of Pediatric Acute Respiratory Distress Syndrome

Summary

Pediatric acute respiratory distress syndrome (ARDS) is a life-threatening clinical syndrome, and dyspnea is its key symptom. Strenuous respiratory effort is a "second hit" for ARDS lungs, inducing changes in regional lung aeration and amplifying lung damage in preclinical studies, a phenomenon known as "patient self-inflicted lung injury". In a clinical setting, clinicians are concerned about the possible connection between dyspnea and ARDS progression based on indirect evidence, such as the worse outcomes associated with delayed intubation or failed weaning from mechanical ventilation. Dyspnea is hard to quantify due to its subjective nature. Still, it can be assessed through its interrelated and independent components: respiratory drive (neural stimuli), respiratory effort (muscle contraction), and work of breathing (energy expenditure).

This project aims to identify mechanical thresholds of dyspnea components to predict early ARDS progression and outcome. The role of respiratory effort is particularly relevant in three phases of ARDS where a transition between spontaneous and controlled ventilation occurs: 1) acute phase, when we try to prevent mechanical ventilation (MV) through non-invasive support; 2) intermediate phase, transitioning from controlled to assisted MV; and 3) late phase, during weaning from MV. These transitions are challenging because it is difficult for clinicians to titrate adequate support and avoid both under- and over-assistance.

In critically ill children, there are no established thresholds for dyspnea components that predict ARDS progression, and it remains unknown whether regional changes in lung aeration can anticipate this clinical deterioration. This is particularly relevant because the oxygenation decline signals that ARDS progression has already occurred, leading to a less reversible condition.

We will use and integrate advanced respiratory monitoring tools to quantify these components, including surface electromyography, occlusion maneuvers, and esophageal manometry. Additionally, electrical impedance tomography, recently adapted for pediatric use, will be employed to detect early changes in regional aeration. All tools used are gold standards for each parameter and allow real-time, bedside measurements without adding invasiveness to usual care.

To test our hypothesis, we will quantify respiratory drive, effort, work of breathing, and regional lung aeration throughout all transitional phases of pediatric ARDS. In the acute phase, drive will be assessed via spectral analysis of surface electromyography, and in intermediate and late phases, via airway occlusion pressure at 100 ms. Esophageal manometry will be used to measure effort (swings of esophageal pressure) and work of breathing (pressure-time product). Changes in regional aeration (overstretching, collapse, and heterogeneity) will be assessed using electrical impedance tomography.

We will define mechanical thresholds and cut-off points for each dyspnea component that predict early ARDS progression and outcomes at each transitional phase. Based on the study results, we envision the future development of algorithms to help guide safer transitions between spontaneous and controlled ventilation, to improve outcomes, and prevent residual morbidity. Our interdisciplinary team of clinicians and biomedical engineers will work to customize respiratory care in critically ill children, optimizing ventilatory assistance across disease stages.

Conditions

• Pediatric Acute Respiratory Distress Syndrome (PARDS)

Interventions

DEVICE

Noninvasive respiratory support

sEMG of respiratory muscles, esophageal manometry, and electrical impedance tomography

DEVICE

Transition from controlled to assisted mechanical ventilation

sEMG of respiratory muscles, esophageal monitoring, and electrical impedance tomography

DEVICE

Weaning from mechanical ventilation

sEMG of respiratory muscles, esophageal monitoring, and electrical impedance tomography

Sponsors & Collaborators

• Pontificia Universidad Catolica de Chile

  collaborator OTHER

• Universidad de los Andes, Chile

  collaborator OTHER

• Universidad Nacional Andres Bello

  lead OTHER

Eligibility

Min Age

1 Month

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-07-13

Primary Completion

2030-03-31

Completion

2030-03-31

Countries

• Chile

Study Locations