SUPPLEMENTAL DIGITAL CONTENT 1 Endogenous Carbon Monoxide Production and Diffusing Capacity of the Lung for Carbon Monoxide in Sepsis-induced ARDS

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SUPPLEMENTAL DIGITAL CONTENT 1

Endogenous Carbon Monoxide Production and Diffusing Capacity of the Lung for Carbon Monoxide in Sepsis-induced ARDS

Yao-Wen Kuo, MD^1,2; R. Scott Harris, MD³; Dean R. Hess, PhD⁴; Paul B. Dieffenbach, MD¹; Augustine M.K. Choi, MD⁵; Laura E. Fredenburgh, MD¹*^‡; Tilo Winkler, PhD⁶*

1 Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Boston, MA; ² Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei City, Taiwan; ³ Vertex Pharmaceuticals, Inc., Boston, MA; ⁴ Department of Respiratory Care, Massachusetts General Hospital, Boston, MA; ⁵ Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY; ⁶ Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, MA

* These authors contributed equally to this work.

‡ Correspondence:

Laura E. Fredenburgh, M.D.

Division of Pulmonary and Critical Care Medicine Brigham and Women’s Hospital

Boston, MA

lfredenburgh@bwh.harvard.edu Phone: (617) 525-9563

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Supplemental Figure 1. Comparison of the Bayesian Information Criterion (BIC) among the four Coburn-Forster-Kane (CFK) models for the time series of inhaled carbon monoxide (iCO) exposures in sepsis-induced ARDS subjects. The CFK models were compared using the Bayesian Information Criterion (BIC) = N * log(MSE) + log(N) * Np, where N is the number of data points (N=5 for time series data), MSE is the mean squared error of the carboxyhemoglobin (COHb) residuals, and Np is the number of estimated parameters. Note the low BIC values of CFK models A and B compared to C and D despite the penalty of the BIC equation for estimating two parameters (A, B:

Np=2) compared to one parameter (C, D: Np=1). CFK model A had the lowest BIC value for most of the 25 iCO exposures, suggesting that this model can characterize the time series data of iCO exposures better than the other models. CFK model B was relatively close to CFK model A in its overall performance. Please refer to Supplemental Table 1 and Supplemental Table 2 in Supplemental Digital Content 2 for detailed values.

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BIC

A B C D

Model

BIC of the four models

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Supplemental Figure 2. Comparison of the Root Mean Square Error (RMSE) among the CFK models for the carboxyhemoglobin (COHb) residuals of the iCO exposures in sepsis-induced ARDS subjects. The RMSE of the CFK model predictions compared to the COHb time series data shows an excellent fit for CFK model A, closely followed by CFK model B. Please refer to Supplemental Table 1 and Supplemental Table 2 in Supplemental Digital Content 2 for detailed values.

0 .5 1 1.5 2 2.5

RMSE (%COHb)

A B C D

Model

RMSE of the four models

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Supplemental Figure 3. Comparison of the estimated diffusing capacity of the lung for carbon monoxide (DLco) among the four CFK models for iCO exposures in sepsis-induced ARDS subjects. DLco estimations higher than 45 were plotted as 45 and considered not converged. Note that CFK model A always converged and that the values of CFK model D were not estimated but set to the subject’s predicted DLco adjusted for hemoglobin. Please refer to Supplemental Table 1 and Supplemental Table 2 in Supplemental Digital Content 2 for detailed values.

not converged

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DLco (ml/min/mmHg)

A B C D

Model

DLCO of the four models