Definitions 1 NERD

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Patients with NERD do not, by definition, have esophagitis and appear to be at low risk to develop esophagitis; NERD is best defined, therefore, on the basis of symptoms and/or their impact on an individual's health-related quality of life (QOL) [4]. Indeed, it is apparent that NERD patients can, and do, suffer from symptoms as severe as those with ERD, and the impact on quality of life can be at least as disabling in NERD as in other manifestations of GERD [5], [6]. It is appropriate, therefore, that recent definitions of GERD incorporate the issue of quality of life [4]. In defining NERD, one must be cognizant of prior therapy; an esophagus rendered free of esophagitis by acid-suppressive therapy does not constitute NERD. Attempts to define GERD on the basis of histological findings, in those in whom the mucosa is endoscopically normal, have also proven disappointing [7], [8].

Fass and colleagues have suggested that NERD may be further defined and sub-classified based on the results of 24-hour pH recordings in to three distinct groups [9] (Fig. 1):

(i) Those with an abnormal acid exposure time (AET); these individuals appear to behave, in terms of therapeutic response, in a manner analogous to those with obvious esophagitis,

Complicated

Reflux

Disease

Complicated

Reflux

Disease

Erosive

Non-Erosive

Reflux

Reflux

Disease

Disease

(ERD)

(NERD)

Fig. 1. GERD subgroups

+ Symptom-

No acid

reflux

association

association

Functional

Sensitive

Heartburn

Esophagus

Fig. 1. GERD subgroups

(ii) Those who demonstrate a normal AET but in whom symptoms and reflux events are significantly correlated (as estimated by some form of symptom index or other measure of symptom-reflux event association); these individuals have been referred to as "the sensitive esophagus" [10],

(iii) Those with typical reflux symptoms (i.e., heartburn and acid regurgitation), yet in whom all parameters of the pH study are normal. These individuals appear highly resistant to acid-suppressive therapy [10] and are more likely to demonstrate psychopathology [11].

The definition of functional heartburn is especially problematic and confusing. For example, the second iteration of the "Rome" criteria [12] and other experts [13]-[15] incorporate groups (ii) and (iii), above, in the definition of functional heartburn. Given that classification should advise diagnostic and therapeutic decisions and predict pathophysiology, most clinicians would reserve this term for group (iii) alone. This is also the opinion of this author; it is, to my mind, counterproductive and well as counterintuitive to include two quite distinct groups of patients (i.e., those who do and do not demonstrate an association with acid exposure and a response to acid suppression) in the same category.

This reliance on pH data could be construed to imply that this test plays a pivotal and essential role in the evaluation of NERD. If one accepts that the true NERD patient (as distinct from the individual with therapeutically-resolved esophagitis) is at low risk for progression to such worrisome complications as Barrett's esophagus, then a therapeutic trial (also referred to as the PPI test) emerges as a valid diagnostic alternative [16]. This approach has the additional benefit of rapidly identifying those who are likely to benefit from long-term PPI therapy.

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