Given such a result, “one might conclude that reflux is contributing to the asthma, when in fact the asthma may be causing reflux.” In that scenario, a positive pepsin test may lead clinicians to focus their treatment strategies on reflux rather than the underlying lung disease.
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December 2013Dr. Bishop added another caveat: It’s possible that the Western blot assay is so sensitive that it is detecting extremely small levels of pepsin in the airways. Thus, one future refinement for this test could be to add more quantitative information. “Could you create, for example, a panel-type test, where a quantitative control is loaded in adjacent ‘lanes’ so that you could see the strength of the band, with different amounts of pepsin shown? That would give you some idea of how much pepsin is being found in the airways relative to the control, and whether that amount is sufficiently higher to denote some connection to the patient’s pulmonary symptoms.”
Dr. Bishop said his own preference for assessing reflux in pediatric patients with chronic lung disease is to have them undergo esophageal pH impedance monitoring. “When patients experience a symptom, they press a button on the recording device, which allows us to correlate those symptoms with the tracing. For us, this gives a better understanding of whether any reflux detected is indeed clinically significant.” But even this test has drawbacks, Dr. Bishop said. For example, the test cannot correlate chronic respiratory symptoms such as vocal hoarseness with individual reflux events, nor are there absolute cutoffs between normal and abnormal studies.
In fact, “all of the standard tests used to detect reflux are imperfect; that’s the problem we are all dealing with,” he said. “So it is important that we explore other methods for assessing reflux and, on that score, this paper is very stimulating and warrants further study.”
More Work Needed
Dr. Kerschner said that Dr. Bishop’s caveats “hit all of the high points” regarding the pepsin test’s current limitations. “We noted in the paper, for example, that our current technique for detecting pepsin in BAL samples can’t be used for quantifying the amount of pepsin present,” he said. “What we essentially showed is that we were able to [develop] a very sensitive identification test for this enzyme. But what does that mean, clinically? The real key will be the next clinical trials that we conduct, not only in children but also in adults, to see if using this test makes a difference in patient outcomes. We think it will.”