First, although intuitively one might consider that size and frequency do matter (pulmonary arteriovenous malformations [PAVMs] are usually larger and more frequent in HHT than in HPS), the literature does not fully support this observation. Initial small studies suggested that neurologic complications in patients with HHT (brain abscess and stroke) are more common in those with more severe or diffuse PAVMs.2,3 However, a cohort study of 219 consecutive patients with HHT and PAVMs showed no clear relationship between the risk of brain abscess or stroke with markers of PAVM severity, including diameter of the largest feeding vessel or degree of right-to-left shunt.4 As mentioned by Dr Salerno, a second potential mechanism has to do with the local microenvironment at the pulmonary vasculature level. The extensive accumulation of pulmonary intravascular macrophages that adhere to the pulmonary endothelium in animal models of biliary cirrhosis is very well known and is believed to be a compensatory mechanism due to the dramatic decrease in the phagocytic capacity of the liver that allows circulating bacteria to enter the pulmonary circulation.5 If a similar phenomenon occurs in humans, we speculate that the increased intravascular macrophage activity could play a role in better bacterial clearance, despite shunting. A third potential mechanism is the common use of antibiotic therapy to prevent spontaneous bacterial peritonitis in patients with HPS compared with patients with HHT. Long-term antibiotic use in these patients may help to further reduce transient bacteremia, decreasing the risk of brain abscesses. Furthermore, it has been shown in experimental models that the use of antibiotics, such as norfloxacin (commonly prescribed in patients with cirrhosis to prevent spontaneous bacterial peritonitis), reduces the severity of intrapulmonary shunting by decreasing the nitric oxide production of the pulmonary intravascular macrophages.6 We agree with Dr Salerno that further prospective studies which include the reporting of cerebrovascular events in the setting of HPS are needed to elucidate this important clinical question.