Although some findings were consistent with prior observations, several are noteworthy. The median GCS among aspirators in this cohort was 13, significantly higher than the dogmatic 8 threshold where elective endotracheal intubation is often considered to prevent aspiration. However, the effect of a single unit increase in GCS is not trivial, resulting in a 23% decrease in the odds of aspiration. Based on this and others,19 there is unlikely to be a single threshold in which the risk of aspiration can be confidently assessed by GCS alone. Another notable negative finding was the lack of relationship between aspiration and clinically diagnosed GERD. GERD is a prerequisite for “gastropulmonary” aspiration,20 but additional “hits,” such as infection, the quantity and nature of the aspirate material, and the host immune response, combine to determine the actual consequence of aspiration.17 While reducing acidity may protect against respiratory complications, PPI did not appear to significantly benefit patients who aspirated. It may be because nonacidic gastric contents are critical and synergistic with acid in the development of lung injury.21‐23 Hence, approaching aspiration as a problem of acid-induced lung injury and treating with acid suppression alone may be inadequate, while potentiating the risk of pneumonia.24 Once aspiration occurs, ACE inhibitors, by increasing the cough reflex,25‐27 may potentially protect against pneumonia28; however, no protective effect was observed in our cohort. Although ACE inhibitors may protect against microaspiration, it is unlikely that a “more sensitive” cough reflex will protect against gross aspiration, as identified and defined in this study. Host response is also likely critical in determining whether clinical pathology develops.17,29,30 As with prior reports, steroids proved possibly harmful,16 but β-blockade appeared to reduce the respiratory sequelae of aspiration in this study. β-blockade has been suggested to be helpful in other conditions with significant systemic inflammatory response31,32; and in one animal model of aspiration, β-blockers protected against pneumonia, bacteremia, and death.33 Thus, host response could potentially be targeted to lessen the clinical consequences of aspiration. In the subgroup within aspirators who did not have any other comorbid predisposing condition for ARDS, it was notable that they were younger, had more GERD, and were less ill as compared with other aspirators with additional risks for lung injury. This confirms, not unsurprisingly, the heterogeneity and complexity of aspirators, and may imply that aspiration could be potentially be viewed as two broad subgroups: one in which aspiration is a “complication” of other acute illnesses, chronic comorbidities, aging, and health-care associated factors, and another in which aspiration is a primary event potentiated by issues directly related to the pathway from the stomach to the airways, such as GERD and swallow function. Distinguishing such phenotypes among aspirators in the future may theoretically be helpful toward systematic investigations trying to identify potential interventions. Finally, it was interesting to note that chest radiation appeared to be independently associated with the risk for aspiration, although we are unable to tease out whether this was an effect of acute radiation injury (eg, to the esophagus, lungs, airways, vagus nerve, mucositis) or whether this is also a potential concern for patients with more distant chest radiation from chronic radiation damage to these same structures. Further investigations on these associations would be of interest.