“Clearly, this shows that LLM testing is not a very sensitive method for assessing these patients,” Dr. Kerschner said. “The pepsin assay, in contrast, was highly sensitive and a reliable marker for AERD.”
Explore this issue:December 2013
LLM Results Not a Surprise
Dr. Kerschner added that it should not be too surprising that the LLM test proved so inferior to the Western blot assay for pepsin. “The LLM test is really a measure of generalized inflammation in macrophages; that’s why it’s such a nonspecific, inaccurate test,” he explained, adding that several previous studies have questioned LLM’s accuracy (Pediatr Pulmonol. 1999;27:419-422).
Why, then, does LLM continue to be used? “Until you actually develop a new, superior test for some physiologic process,” he said, “it’s very hard to underscore the shortcomings of the current screening method.”
In terms of next steps, Dr. Kerschner said that his team plans on submitting a grant for a more extensive clinical trial to the National Institutes of Health, which they hope will strengthen the link between pepsin, aspiration and clinically significant chronic lung disease. “But my own feeling is that this test is ready for prime time now,” he said. “In fact, if you are a believer in what came out of this study, it would suggest that pulmonary physicians who routinely order the LLM test in children when they present to the OR for a bronchoscopy as a means of detecting aspiration should probably stop getting the test and order ours.” Dr. Kerschner’s team is exploring ways to make the test commercially available.
In Absence of Causality, Caution Urged
Warren Bishop, MD, professor of pediatrics at the University of Iowa Carver College of Medicine, and director of the division of pediatric gastroenterology at the University of Iowa Hospitals and Clinics in Iowa City, agreed that the Western blot assay for pepsin is very promising. But what is missing in the current study, he said, “is any clinical correlation between the presence of pepsin and the chronic respiratory symptoms in their subjects,” he said. Thus, he added, “It is very hard to definitely say that pepsin is an effective test to document clinically significant extraesophageal reflux disease that contributes to those symptoms.”
There’s also a “chicken-and-egg” factor to consider, Dr. Bishop said. Some chronic respiratory disease “actually can cause reflux and potentially aspiration,” he explained. “Asthma is a good example; negative chest pressure and an increased work of breathing can trigger the reflux of stomach contents into the airways, which could lead to a positive pepsin test.”