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This presentation (dyspnea, productive cough, hypoxemia, expiratory wheezing, accessory muscle use, smoking history) is consistent with a COPD exacerbation. Supplemental oxygen may be warranted for significant hypoxemia, but excessively high oxygen concentrations can lead to increased CO2 retention (oxygen-induced hypercapnia), causing confusion and depressed consciousness. The major cause is increased ventilation-perfusion mismatch: hypoxia normally causes vasoconstriction of pulmonary arterioles, shunting blood toward well-ventilated alveoli and minimizing physiologic dead space. High-concentration oxygen raises oxygen levels in poorly ventilated regions, reversing this vasoconstriction; the redistribution of blood flow away from well-ventilated alveoli increases physiologic dead space and reduces CO2 excretion. (Choice A) Oxygen alleviates hypoxic pulmonary vasoconstriction, decreasing pulmonary vascular resistance. (Choice B) Hyperoxia can increase reactive oxygen species and cause oxygen toxicity (substernal heaviness, pleuritic chest pain, cough/dyspnea within 24 hours of breathing pure oxygen), but that is not the cause here. (Choice C) In hypercapnia and respiratory acidosis the kidneys increase bicarbonate reabsorption over days, which would ameliorate hypercapnia. (Choice D) High-flow oxygen reduces peripheral chemoreceptor stimulation, decreasing (not increasing) respiratory rate and minute ventilation.

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