Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS

Rebecca M. Baron; Antonio Arciniegas; Susan Sullivan; Michelle Courchaine; B. Taylor Thompson; Alex Stenzler; Mary E. Choi; Augustine M.K. Choi; Mark A. Perrella; Tilo Winkler

doi:10.1186/s12931-026-03668-5

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Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS

Journal article

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Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS

Rebecca M. Baron, Antonio Arciniegas, Susan Sullivan, Michelle Courchaine, B. Taylor Thompson, Alex Stenzler, Mary E. Choi, Augustine M.K. Choi, Mark A. Perrella and Tilo Winkler

Respiratory research, Vol.27(1), 212

05/28/2026

DOI: 10.1186/s12931-026-03668-5

PMID: 42210269

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Abstract

Background Low-dose inhaled carbon monoxide (iCO) has demonstrated significant therapeutic potential in preclinical studies, and its safety has been established in human studies. However, the safety of delivering personalized iCO concentrations of 200 to 500 ppm in ventilated patients with pneumonia and ARDS, targeting 7% HbCO at 90 min of exposure, remains unknown. Methods Personalized iCO concentrations needed to reach a plasma HbCO of 7% at 90 min were determined using a Coburn-Forster-Kane (CFK) calculator, utilizing baseline and 20-minute (20-min) arterial HbCO measurements at an iCO test concentration of 200 ppm. The personalized iCO concentration was administered for the remainder of the 90 min with HbCO measurements performed at 60-, 75-, and 90-minutes. Results There were no safety incidents observed during the study, and all exposed subjects were alive and well at 6-month follow-up. Surprisingly, we found significant deviations between measured and predicted HbCO levels at 90 min for individualized exposures with iCO of 220 to 425 ppm (p < 0.001), which were more discrepant at higher iCO doses. However, fitting the CFK model to the 20- to 90-minute HbCO measurements confirmed the validity of the CFK model and revealed significant deviations for baseline HbCO (p < 0.001), suggesting pulmonary vascular responses to iCO during the 20-min test exposure, confirmed by observed changes in DLCO. Conclusions Pulmonary vasodilation in response to iCO can affect early HbCO kinetics, which is relevant to refining protocols for reliable, personalized iCO administration that optimize pulmonary iCO concentrations, thereby increasing the benefits of therapeutic iCO administration in lung diseases.

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Title: Subtitle: Relevant insights from personalized inhaled carbon monoxide dosing in a safety study in pneumonia and ARDS
Creators: Rebecca M. Baron - Brigham and Women's Hospital
Antonio Arciniegas - Brigham and Women's Hospital
Susan Sullivan - Brigham and Women's Hospital
Michelle Courchaine - Brigham and Women's Hospital
B. Taylor Thompson - Boston, MA USA
Alex Stenzler - Applied Technologies (United States)
Mary E. Choi - Cornell University
Augustine M.K. Choi - Weill Cornell Medicine
Mark A. Perrella - Brigham and Women's Hospital
Tilo Winkler - Massachusetts General Hospital
Resource Type: Journal article
Publication Details: Respiratory research, Vol.27(1), 212
DOI: 10.1186/s12931-026-03668-5
PMID: 42210269
ISSN: 1465-9921
eISSN: 1465-993X
Publisher: BMC
Language: English
Date published: 05/28/2026
Academic Unit: Radiology; Anesthesia
Record Identifier: 9985166870502771

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