How helpful is a pH-Impedance Study in Identifying Reflux-Induced Symptoms?

In both kids and adults, individuals presenting with complaints of reflux more often have other problems like functional heartburn or reflux hypersensitivity (see posts below).  A recent prospective, cross-sectional study (LB Mahoney et al. JPGN 2020; 70: 31-36) provides data that further shows that abnormal pH-impedance (pH-MII) testing does NOT predict reduced quality of life (QOL) in children with reflux symptoms (n=82).

Key findings:

  • 38% had abnormal pH-MII testing; however, there were no significant differences in QOL scores on any of the tested questionairres between those with normal or abnormal pH-MII studies.
  • Subjects with gross esophagitis on EGD reported significantly worse QOL scores. Microscopic esophagitis was not associate with differences in QOL scores.

The implication of this study is that reflux without esophagitis is NOT a driver of abnormal QOL parameters; instead, functional GI disorders are likely more important.

My take: This study makes it clear that gross endoscopic findings are much more consequential than abnormal pH-MII studies.

Related blog posts:

pH Probe Testing: Rumors of My Death are Premature

Several years ago, an “obituary” was written for the pH probe (Putnam PE,J Pediatr.  2010; 157(6):878-80) due to the presumed superiority of pH-impedance (pH-MII) studies in detecting gastroesophageal reflux disease (GERD)  As noted in previous blogs (see below), there have remained a number of concerns with the assumption that pH-MII is an improvement over pH studies without impedance.  Several recent studies elaborate on those concerns:

  1. Cheng F-K F, et al. Clin Gastroenterol Hepatol 2015; 13: 867-73
  2. Patel A, et al. Clin Gastroenterol Hepatol 2015; 13: 884-91
  3. Vaezi MF. Clin Gastroenterol Hepatol 2015; 13: 892-94 (editorial)

In the first study, the authors identified 221 patients and retrospectively reviewed GERD testing from 2006-2011.  Prior to testing, 97% had received prescribed PPIs before testing; however, PPIs were discontinued for at least 1 week prior to evaluation which included upper endoscopy, esophageal manometry, and pH-MII.

  • 21 (10%) had erosive esophagitis
  • 61 (27%) had nonerosive reflux disease with increased pH
  • 18 (8%) had nonerosive reflux disease with abnormal impedance
  • 30 (14%) had hypersensitive esophagus
  • 18 (8%) had functional heartburn
  • 30 (14%) had other functional disorders
  • 43 (19%) were undetermined

Thus, this retrospective study showed that the majority (roughly 2/3rds) of patients with GERD symptoms on PPI therapy did not have GERD based on objective testing.  The authors chose to test off PPI therapy “because we postulated that the pretest probability of GERD diagnosis was low, primarily given their lack of response to PPI.”

In the second study, 187 subjects (≥18 years) underwent pH-MII testing in a prospective study from 2005-2010.  49.7% were tested off proton pump inhibitor therapy. Abnormal acid exposure time consistently predicted symptomatic outcome.  The authors note that performing pH-MII off PPI therapy best predicts response to antireflux therapy

In the third reference, the editorial which commented on the second, there are several useful points:

  • “There is little doubt that pH-impedance testing provides a more sensitive means of comprehensively identifying reflux events in a given patient. However, to date, studies have failed to demonstrate that it provides any significant additional clinical benefit.”
  • “Caution must be exercised when incorporating the added objective data from non-acidic or weakly acidic reflux events into treatment decision-making…Studies including Patel et al have not shown that knowledge regarding continued non-acid or weakly acid reflux events alter patient outcomes.”
  • “Wireless pH testing is generally better tolerated and provides longer measurement duration”
  • The use of symptom indices are too subjective.  “Recent data question the use of these indices especially in those with refractory symptoms and minimal reflux by pH or impedance testing.”  SI and SAP could be altered by chance occurrences….”A colleague expert in esophageal diseases …once said: “I know the tests are no good but I don’t know what else to use.'”
  • “Let us simplify our approach on the basis of available data and not use measures that we know are suboptimal at best.”

After looking at these studies and the previous pH probe obituary, I’m reminded of a story.  Several religious leaders were asked what they wanted someone to say at their funeral.  A few stated that they wanted their congregants/flock to comment on their values, like piety and charity.  However, one said, “I hope they say, ‘Look he’s moving!'”

Bottomline: There is no reliable evidence that pH-MII testing improves outcomes over conventional pH probe testing. In fact, the use of pH-MII, by lowering the specificity for GERD, could have a detrimental effect.  With either test, holding acid suppression for 1 week (with PPIs) is likely to be helpful in interpreting the results.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Zoo Atlanta

Zoo Atlanta

Trouble Sleeping and Gastroesophageal Reflux

Determining whether reflux is causing an infant to have trouble sleeping is quite difficult as a practical matter.  A recent retrospective study adds information to this topic but opens up a can of worms (JPGN 2013; 56: 431-35).

The main problem is that clinical reflux occurs in the majority of infants and that sleeping problems are ubiquitous as well.  This leaves the door open to testing a lot of infants. At the  same time, effective therapeutic options are limited.  So, identifying that reflux is causing trouble sleeping, when feasible, may be akin to getting the license plate of the truck that ran you over.

In this retrospective study (2008-2010) of 24 infants with a median age of 5 months, 18 were receiving acid-suppressing medications prior to evaluation.  Determination that reflux was causally associated with awakenings and arousals was determined with symptom association probabilities (SAP) based on 2-minute measurement intervals with multichannel intraluminal impedance/pH monitoring/simultaneous polysomnography; SAP was considered significant if ≥95%.

Findings: Seven patients had a positive SAP for arousals due to GER (5 exclusively related to non-acid GER).  Nine patients had a positive SAP for awakenings due to GER (4 exclusively related to non-acid GER).

There were several limitations of the study.  Besides the small size, the main limitation of this retrospective study was a selection bias.  Other limitations included a large number of patients with comorbid conditions and the coincident usage of acid-suppressing medications.  19 of 24 patients had one or more significant comorbid conditions: laryngomalacia in 10, prematurity in 5, genetic syndromes in 3, esophageal atresia in 1, and SLE in 1.

Take-home point: This study is in agreement with the general consensus that GER (acid and non-acid) may trigger sleep interruptions in infants. Nevertheless, given the lack of impact on management, only rarely will infants with poor sleep benefit from these investigations.

Related blog entries:

Why didn’t patient with documented reflux get better with PPI?

There are numerous problems with pH studies; many of these problems have been alluded to in previous blog entries (see below).  Another problem is that these studies are not highly predictive of response to therapy (Gut 2012; 61: 501-506).

This French study from three centers examined 100 consecutive patients (58 females) with an average age of 50 years.  All patients had reflux symptoms, namely regurgitation and/or heartburn.  PPI dosage was not standardized and reflux symptoms were quantified with recall questionnaires.

The authors note that up to 40% of patients with reflux symptoms have inadequate symptom relief with a 4-week course of single dose proton pump inhibitor (PPI) therapy; the aim of their study was to investigate which factors on pH probe-impedance (pH-MII) would predict a response to therapy.

Definition: Nonresponders were patients who had more than 2 days of mild symptoms per week while receiving a standard or double dose of PPI treatment for 4 weeks


  • No reflux pattern on pH-MII was associated with a response to PPIs. Table 2 in the study looked at multiple factors including SI, SAP, time for acid exposure, and number of reflux events.
  • Lower BMI (≤ 25 kg/m-squared), non-erosive reflux, and normal pH study were associated with poor PPI response
  • Other factors associated with poor PPI response: female gender, irritable bowel syndrome (IBS), and functional dyspepsia.
  • Response rates: 58% of individuals with BMI >25, 71% with esophagitis, 23% with functional dyspepsia, 30% with IBS
  • Among responders, 77% were receiving a single dose PPI

Some of the poor response may be related to the study population.  Only 35% had abnormal acid exposure.  In total, 67% were determined to have abnormal pH studies, though this was due to a large fraction having a positive symptom-reflux association analysis.

However, this study population likely reflects a typical clinical group of patients diagnosed with GERD and demonstrates some of the shortcomings of pH-MII in clinical practice.  Even patients with abnormal pH-MII studies, the presence of functional dyspepsia and IBS were strongly associated with PPI failure.

Previous related blog entries:

HEROES trial

Impedance recommendations from PIG

Gastroesophageal Reflux: I know it when I see it

Treating reflux does not help asthma

Unexplained chest pain

Impedance recommendations from PIG

The ESPGHAN Pediatric Impedance Group (PIG) has published a review/consensus statement on the use of pH-Impedance monitoring (MII-pH) in children (JPGN 2012; 55: 230-34).

Conclusions from this group:

  • MII-pH provides more information than conventional pH probe.  Whether this information will “inform prognosis, or predict response to therapy in pediatric patients has yet to be determined”
  • ‘As long as there is no effective medical therapy for weakly acid and nonacid reflux, the clinical relevance of MII-pH remains debatable’
  • “There are no data on the results of antireflux surgery based solely on the detection of weakly acid and nonacid reflux”
  • MII-pH is investigational technique needing standardization before routine diagnostic use can be recommended.
  • Major indications: need to identify weakly acid and nonacid reflux, persisting symptoms during antireflux treatment, use in identifying rumination syndrome, and research
  • Limitations of MII-pH: high cost, limited contribution to change in medical care, lack of evidence-based parameters for assessment of GER

Related blog entries:

Gastroesophageal Reflux: I know it when I see it

Treating reflux does not help asthma

The Medical Pendulum and Gastroesophageal Reflux

Gastroesophageal Reflux: I know it when I see it

      According to Wikipedia, Justice Potter Stewart, in Jacobellis v. Ohio 378 U.S. 184 (1964) stated the following: I shall not today attempt further to define the kinds of material I understand to be embraced within that shorthand description [“hard-core pornography”]; and perhaps I could never succeed in intelligibly doing so. But I know it when I see it, and the motion picture involved in this case is not that. [Emphasis added.]
     To some extent, ‘I know it when I see it’ has been the mantra about identifying gastroesophageal reflux for advocates for pH-impedance (pH-MII).  Enthusiasts have claimed that pH-MII is vastly superior to pH studies alone for many reasons including the ability to detect more GER episodes than conventional pH studies.  Yet, a major flaw has been a paucity of normative data.  To determine whether there is interobserver and intraobserver agreement in the interpretation of pH-MII, seven expert world groups collaborated on a study to analyze ten pediatric 24-hour tracings (J Pediatr 2012; 160: 441-6).
     Five of these studies were considered easy and five were more challenging due to less obvious features like low baselines, retrograde patterns during swallowing, and moving/crying artifacts.   Among 1242 liquid and mixed GER events, 490 (42%) were scored by the majority of observers.  The authors claim that this is “moderate agreement.”  The automated analysis (AA), not surprisingly, had much better agreement than manual analysis.   With AA there was 94% sensitivity rate and 74% specificity. When looking at AA alone, AA missed 6.5% of events scored by observer consensus and  30% of GER episodes recorded with AA were not detected by majority consensus.
     When looking at each pH-MII recording (Figure 2), there was poor agreement on whether the study was pathologic.  Only five of the studies had uniform agreement that the number of episodes (>73 GER episodes) were either pathologic or not. Those with agreement were all negative studies.  The authors conclude, though, that there was “substantial” agreement based on a mean kappa value of 0.70.
     A comparison to a previous pH-MII publication (Scand J Gastro 2011; 46: 271-6) notes that in this previous study, 83% of pH-MII recordings had a concordant symptom association probability despite underdetection of GER episodes with AA; it was recommended to use ‘AA when the symptom association was positive.  If symptom association was negative, they suggested manual analysis.’
    The conclusions from the current study:
  • ‘In theory, AA is favored over manual analysis due to reproducibility’
  • AA does not seem specific enough to ensure correct marking of GER episodes in infants and children yet
  • Consensus to refine AA needs to be reached …to retain confidence …in impedance

If this is the best that worldwide experts can do with this widespread technology, what does that mean for clinicians in practice?

Additional references:

Recent related posts:

The Medical Pendulum and Gastroesophageal Reflux

Unexplained chest pain

  • -Journal of Gastroenterology and Hepatology 2010;25:817-22. Has some normative pH-MII data.  ‘Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study.’
  • -JPGN 2010; 50: 25. Reflux detected by Impedance does NOT determine fundoplication outcome. n=34.
  • -JPGN 2010; 52: 129. Review. No normative data. Using SAP>95% to correlate symptoms (better than SI or SSI). Main use is to study intractable pts to establish if nonacid reflux is contributing to symptoms.
  • -J Pediatr 2010; 157: 878 (“death of pH probe”), 949. Use of impedance in children. n=225. (70 were discarded). Notes lack of therapeutic possibilities for non-acid reflux.  Symptom index is + if >50%, SAP if >95%. Symptom index is number of symptoms with reflux episode divided by total number of symptom occurrences. SAP, symptom association probability, is a statistical tool that uses 2-minute windows throughout recording to correlate symptom and reflux event.  pH probe 2nd metal for infant -place 2cm above LES.  pH probe 3rd metal for child -place 3cm above LES
  • -Clin Gastro & Hep 2009; 7: 743. n=39 adults. Non-acid reflux events in patients on therapy correlated with acid reflux parameters when patients studied off therapy. Abnormal impedance parameters: total number of reflux events >63 (avg normal was 28). This study relied on # of reflux events more than SAP or SI. SAP or SI is problematic in patients who lack clinical response to PPIs.
  • -Gastroenterology 2009; 136 (suppl 1): S1896. n=143. #of events (not SI or SAP) is then most conservative estimate as well as the one with the highest likelihood of encompassing other symptom assoication parameters.
  • -J Pediatr 2009; 154: 248. n=50. a high # with normal pH had symptom correlation w GER events. (initial cohort was 80 –30 excluded due to problems with study or insufficient symptoms) SAP is superior for correlating symptoms.
  • -Clin Gastro & Hep 2008; 6: 840. Impedance is best tool -D Castell.; -Clin Gastro & Hep 2008; 6: 880.
  • -Clin Gastro & Hep 2008; 6: 482, 521. ‘Impedance/pH is best tool’. Pts who respond to PPIs likely due so due to its effect on chemostimulation; those who continue with symptoms may do so based on mechanostimulation -related to volumes in esophagus not due to acidity.
  • -J Pediatr 2006; 149: 216. Equal frequency of acid and non-acid reflux in 24 pts with asthma. No correlation identified with resp symptoms.
  • -Clin Gastro & Hep 2006; 4: 167. Impedance does not add to pH probe in UNTREATED patients.
  • -JPGN 2002; 34: 511, 519.
  • -Pediatrics 2006; 118: e299, 793. Impedance data in preterm infants. Asymptomatic and affected infants with similar impedance values and both have reflux to upper esophagus.