tracings quite difficult [49].
Figure 9.12 Impedance changes in ohms during reflux of gas, liquid, and mixed contents, obtained with a catheter incorporating six impedance measuring segments (Z1–Z6), which are shown on the y‐axis. Impedance values for the second measuring segment (Z2) are shown for the three reflux episodes. (A) Reflux of gas is characterized by sharp increases in impedance beginning in the most distal recording segment and rapidly progressing upward toward the proximal esophagus. In Z2, impedance rises from a baseline of 1360 ohms to a peak of 10,000 ohms. (B) Reflux of liquid is characterized by sequential impedance falls, starting in the distal esophagus and moving upward toward the mouth. In Z2, impedance falls from a baseline of 3600 ohms to a trough of 260 ohms. (C) Reflux of gas mixed with liquid. In Z2, impedance rises from a baseline of 2860 ohms to a peak of 10,000 ohms; this is followed by an impedance fall to a trough of 350 ohms.
In summary, MII–pH enables refined characterization of the reflux episode. Because it measures both volume presence (through MII) as well as changes in acidity (through pH), it enables detection of reflux of all types—acid, nonacid, and re‐reflux—while providing details about the volume and acid clearance, as well as the composition and height reached by the refluxate.
Clinical applications
There is a growing body of work showing the clinical applications of MII–pH monitoring both in pediatric and adult patients, the details of which are discussed in Chapter 19. In short, with its ability to measure not only acid but also nonacid reflux, MII–pH monitoring shifts the GER testing paradigm: reflux events are no longer detected by pH alone. Instead, the presence, distribution, and clearing of refluxate is primarily detected by MII, and characterized as acid versus nonacid based on pH change and as liquid, gas, or mixed based on MII. Because of its enhanced ability to detect and characterize GER, MII–pH has evolved into a clinically useful tool, especially for the evaluation of persistent symptoms despite acid suppression, an increasingly frequent clinical problem.
Assessment of mucosal integrity using baseline impedance measured by MII‐pH catheter
One of the major limitations of MII–pH is that it only provides a 24‐hour snapshot of a disease process that is chronic in nature, and so it fails to account for day‐to‐day variability of reflux [50]. Patients with GERD or eosinophilic esophagitis (EoE) have dilations of intercellular space (DIS) between esophageal epithelial cells, which are regulated by tight junction proteins. DISs are filled with electrolyte‐rich fluid, a good conductor of electrical current, leading to a low‐impedance signal [51–56, 67]. The degree of DIS is shown to inversely correlate with MI measurements in adult [68] and pediatric [69] populations, showing that MI could serve as a surrogate marker of histological changes in these patients. Consequently, the assessment of persistently impaired mucosal integrity associated with non‐erosive mucosal damage may provide a better surrogate for the evaluation of GERD. Lower baseline intraluminal impedance among patients with esophagitis and NERD has been demonstrated in observational studies. In a study of 35 GERD patients and 17 functional heartburn patients, mucosal impedance was measured during MII–pH testing at night during a period of at least 30 min with a stable baseline activity. Baseline impedance in GERD patients was lower than in those with functional heartburn. Further, an inverse association demonstrated in esophageal biopsies between dilated epithelial intercellular spaces and baseline impedance in the distal esophagus, suggesting a physiologic correlation. Perhaps most striking was that, using a cutoff value of 2100 Ω, baseline impedance identified GERD patients with a positive and negative predictive value of 75% [57].
Figure 9.13 Novel MI balloon catheter with 36 channels measuring impedance axially and radially along a 10 cm length of the esophagus.
Source: Courtesy of Dr. David Katzka.
In addition, patients with hypersensitive esophagus have been shown to have significantly lower baseline impedance than healthy controls with similar acid exposure time. Furthermore, in one study of 48 GERD patients, median baseline impedance increased from 886 to 1372 Ω after PPI administration. In addition, baseline impedance was significantly lower in a cohort of 30 patients with PPI‐responsive functional heartburn compared with those without PPI response [58, 59]. In another study of heartburn patients, a baseline impedance value of 2446 Ω had a positive predictive value of 82% and a negative predictive value of 96% for identifying PPI‐responsive patients [60]. These studies suggest that baseline impedance in patients with functional heartburn and esophageal hypersensitivity may predict therapeutic outcomes. On the other hand, patients with Barrett’s esophagus have more permeable columnar mucosa and so low baseline impedance [61]. This was confirmed in a cohort of 10 patients after radiofrequency ablation in which baseline impedance was low before treatment but increased after squamous regeneration [62].
Direct mucosal impedance measurement
Measurement of esophageal mucosal impedance with a transnasal catheter can be subject to error due to lack of adequate contact with mucosa, intraluminal fluid, and catheter movement [63]. In addition, it is well known that transnasal catheter‐based testing is associated with significant patient discomfort (nose pain, throat pain, cough, chest discomfort), which can lead to alteration in patients’ daily activities (less likely to be active, more difficulty with swallowing, and more likely to skip meals), leading to variable sensitivity of the reflux testing [64, 65]. Thus, a new balloon MI catheter system was developed to diminish measurement variability by incorporating both radial and axial sensors mounted on a balloon to measure esophageal mucosal integrity. The initial design included four axial columns of 9 impedance channels (total of 36) separated by 90‐degree intervals with length of 10 cm mounted on an inflatable balloon (Figure 9.13) [66]. The most recent modification included reduction to two axial columns of 9 channels (total of 18) separated by 180‐degree intervals on the balloon. The MI balloon is introduced into the esophagus through the mouth under endoscopic guidance with the most distal sensors just above the SCJ. Direct contact of the MI sensors with the esophageal epithelium is obtained by inflating an intra‐esophageal balloon assembly in a controlled fashion using a calibrated inflation device [66]. In an initial study of 23 patients with NERD, 27 patients with functional heartburn, and 19 patients with erosive esophagitis, median mucosal impedance was significantly lower in patients with erosive esophagitis. Further, patients with erosive esophagitis and NERD had significantly lower mucosal impedance compared with those with functional heartburn. Also noteworthy was that mucosal impedance showed a graded increase from the distal to the proximal esophagus in patients with objective evidence of GERD, reflecting greater acid exposure distally. Mucosal impedance also showed good predictive value for identifying patients with GERD, with a sensitivity of 88% and a specificity of 65% when using a threshold of 3200 Ω. Perhaps most importantly, the authors demonstrated that this approach was feasible in clinical practice, noting that it added only 2 min to the procedure time [70].
In EoE, mucosal impedance may also play an important role in the assessment of mucosal integrity [71]. In one study, patients with active and treated EoE demonstrated a significant increase in impedance after treatment (2574 vs. 6618 Ω, P <0.01) corresponding to measurements made on biopsy. These findings suggest that histologic response to therapy in EoE results in mucosal healing and a decrease in trans‐epithelial molecule flux, which is a restoration of mucosal integrity [72]. A recent study confirmed the clinical utility of direct mucosal impedance measurement in the assessment of EoE activity, with an inverse correlation between esophageal eosinophil