| Summary: | Investigation of pulmonary gas exchange efficacy usually requires arterial blood gas analysis (aBGA) to determine arterial partial pressure of oxygen (mPaO<sub>2</sub>) and compute the Riley alveolar-to-arterial oxygen difference (A-aDO<sub>2</sub>); that is a demanding and invasive procedure. A noninvasive approach (AGM100), allowing the calculation of PaO<sub>2</sub> (cPaO<sub>2</sub>) derived from pulse oximetry (SpO<sub>2</sub>), has been developed, but this has not been validated in a large cohort of chronic obstructive pulmonary disease (COPD) patients. Our aim was to conduct a validation study of the AG100 in hypoxemic moderate-to-severe COPD. Concurrent measurements of cPaO<sub>2</sub> (AGM100) and mPaO<sub>2</sub> (EPOC, portable aBGA device) were performed in 131 moderate-to-severe COPD patients (mean ±SD FEV<sub>1</sub>: 60 ± 10% of predicted value) and low-altitude residents, becoming hypoxemic (i.e., SpO<sub>2</sub> < 94%) during a short stay at 3100 m (Too-Ashu, Kyrgyzstan). Agreements between cPaO<sub>2</sub> (AGM100) and mPaO<sub>2</sub> (EPOC) and between the O<sub>2</sub>-deficit (calculated as the difference between end-tidal pressure of O<sub>2</sub> and cPaO<sub>2</sub> by the AGM100) and Riley A-aDO<sub>2</sub> were assessed. Mean bias (±SD) between cPaO<sub>2</sub> and mPaO<sub>2</sub> was 2.0 ± 4.6 mmHg (95% Confidence Interval (CI): 1.2 to 2.8 mmHg) with 95% limits of agreement (LoA): −7.1 to 11.1 mmHg. In multivariable analysis, larger body mass index (<i>p</i> = 0.046), an increase in SpO<sub>2</sub> (<i>p</i> < 0.001), and an increase in PaCO<sub>2</sub>-PETCO<sub>2</sub> difference (<i>p</i> < 0.001) were associated with imprecision (i.e., the discrepancy between cPaO<sub>2</sub> and mPaO<sub>2</sub>). The positive predictive value of cPaO<sub>2</sub> to detect severe hypoxemia (i.e., PaO<sub>2</sub> ≤ 55 mmHg) was 0.94 (95% CI: 0.87 to 0.98) with a positive likelihood ratio of 3.77 (95% CI: 1.71 to 8.33). The mean bias between O<sub>2</sub>-deficit and A-aDO<sub>2</sub> was 6.2 ± 5.5 mmHg (95% CI: 5.3 to 7.2 mmHg; 95%LoA: −4.5 to 17.0 mmHg). AGM100 provided an accurate estimate of PaO<sub>2</sub> in hypoxemic patients with COPD, but the precision for individual values was modest. This device is promising for noninvasive assessment of pulmonary gas exchange efficacy in COPD patients.
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