The authors also found concentrations of indirect bilirubin to be elevated after sleep in patients with OSA, suggesting that the sleep-related increase in CO is due to the induction of the heme oxygenase (HO) system. CO can be produced endogenously by the breakdown of heme into CO, biliverdin (subsequently degraded to bilirubin), and iron by HO.5 There are constitutively active isoforms of HO, but HO-1 is inducible and its byproduct CO has been suggested as a marker of the activity of the enzyme. HO was initially thought to have only a “housekeeping” role (ie, scavenging and breaking down free heme). However, several other observations suggested that it might have greater importance. For example, HO has a conserved structure across species (even those without circulating heme), it exists in organs not thought to play a role in heme degradation, and, most importantly, its function can be induced by cellular stressors such as inflammation and infection. The HO products CO and bilirubin are now understood to be mediators and effectors that promote cytoprotection via antiinflammatory, antiapoptotic, and antiproliferative effects, and also invoke antioxidant responses. Thus, the HO system is now thought to be protective from a variety of cellular insults.