# Physiologic Predictors of Respiratory Failure in Patients Presenting with Dyspnea

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $89,488

## Abstract

Project Summary
Presentations of respiratory failure can vary from mild requiring supplemental oxygen to more severe
requiring invasive mechanical ventilation (i.e., acute respiratory distress syndrome or ARDS). Early in
respiratory failure patients often have abnormalities in gas exchange, control of breathing, and/or pulmonary
mechanics. During the ongoing COVID-19 pandemic, some studies have demonstrated that increased
respiratory drive is associated with worse clinical outcomes while others have demonstrated contrary findings.
We have also demonstrated that a noninvasive assessment of gas exchange using the alveolar gas meter
(AGM) is predictive of who will require supplemental oxygen from COVID-19 infection. Additional studies
predating the COVID-19 pandemic showed that increased inspiratory effort, large transpulmonary pressure
changes, and elevated dead space were all associated with worse outcomes in ARDS. However, many of
these studies focused on patients already intubated and mechanically ventilated. Less is known about the
relevance of these parameters in spontaneously breathing individuals. For a few years now the notion of
patient self-inflicted lung injury (P-SILI) has been gaining traction in the medical literature. The basic concept is
that patients with impending respiratory failure from existing lung injury can cause worsening damage to their
lungs. If patients are spontaneously breathing with excessively high respiratory drive, then they may generate
excessively negative inspiratory efforts leading to major transpulmonary pressure changes. The results of
these abnormalities are large tidal volumes like mechanically ventilating someone with injurious tidal volumes
prior to the advent of low tidal volume ventilation (LTVV). Also, retrospective review of large cohort studies and
randomized controlled trials of ARDS patients have demonstrated that spontaneously breathing patients prior
to intubation often generated excessively large tidal volumes. Whether their subsequent lung injury was
entirely due to their underlying ARDS pathology or partially due to superimposed P-SILI is not known. If a
physiological signature of impending respiratory failure in spontaneously breathing individuals exists and it is
associated with elevated respiratory drive, steps can subsequently be taken to mitigate the increased drive and
study the longitudinal effects of these variables in patients who develop respiratory failure. Moreover, if such a
signature exists and intervention abrogates some of the subsequent lung injury, this is a strong proof of
concept for P-SILI in vivo. We aim to test three independent but related hypotheses. First, the AGM is a novel
and simple technique which can be used to identify patients at increased risk for respiratory failure better than
traditional metrics. Second, the breath hold maneuver is a validated technique to assess control of breathing
that can identify patients with poor respiratory prognosis. Third, the air...

## Key facts

- **NIH application ID:** 10843751
- **Project number:** 5F32HL167551-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** William Cameron McGuire
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $89,488
- **Award type:** 5
- **Project period:** 2023-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10843751

## Citation

> US National Institutes of Health, RePORTER application 10843751, Physiologic Predictors of Respiratory Failure in Patients Presenting with Dyspnea (5F32HL167551-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10843751. Licensed CC0.

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