The potential of pepsin as a biomarker of supraesophageal GERD has been reviewed (L. Kia, MD; J. Pandolfino, MD; P. J. Kahrilas, MD; unpublished data, 2015). One emerging problem with assaying for pepsin in the tracheobronchial tree is that, currently, available pepsin assays are not specific to pepsin A, the isoform found exclusively in the stomach. Other pepsin isoforms, mainly pepsin C (measured as its precursor pepsinogen C), are also produced in the lungs, pancreas, and seminal vesicles, thereby limiting specificity of pepsin as a biomarker for gastric juice. Moreover, most studies evaluating pepsin as a biomarker for GERD used assays that did not discriminate between these isoforms. In this issue of CHEST (see page 333), Hallal et al7 aimed to address this problem. They report on 34 children on mechanical ventilation in the ICU. The children were studied with 24-h pH-impedance monitoring, and tracheal secretion samples were collected and assayed for pepsin A and pepsin C. All patients tested positive for pepsin A in their secretions, while 76.5% tested positive for pepsin C. All patients also had multiple episodes (median, 60; interquartile range, 20-85) of weakly acidic reflux extending to the proximal esophagus. Moreover, three of the 15 children not on acid-suppressive therapy during the pH-impedance study had substantial acid reflux (13%, 14%, and 45% distal acid-exposure times). Based on these findings, the authors concluded that gastric aspiration is nearly universal in critically ill pediatric patients who are mechanically ventilated and may contribute to the development of pulmonary complications such as ventilator-associated pneumonias.