Multichannel intraluminal impedance-pH and psychometric properties in gastroesophageal reflux: systematic review

Gonçalves, Emília Silva; Assumpção, Maíra Seabra de; Servidoni, Maria Fátima Correa Pimenta; Lomazi, Elizete Aparecida; Ribeiro, José Dirceu

doi:10.1016/j.jped.2020.01.005

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Review article • J. Pediatr. (Rio J.) 96 (6) • Nov-Dec 2020 • https://doi.org/10.1016/j.jped.2020.01.005 copy

Multichannel intraluminal impedance-pH and psychometric properties in gastroesophageal reflux: systematic review^✰ ✰ Please cite this article as: Gonçalves ES, Assumpção MS, Servidoni MF, Lomazi EA, Ribeiro JD. Multichannel intraluminal impedance-pH and psychometric properties in gastroesophageal reflux: systematic review. J Pediatr (Rio J). 2020;96:673–85.

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective:

Systematically assess studies that have analyzed the psychometric properties of multichannel intraluminal impedance-pH for the diagnosis of gastroesophageal reflux. Systematically verify studies that have analyzed the psychometric properties of multichannel intraluminal impedance-pH regarding the diagnosis of gastroesophageal reflux disease in pediatric patients.

Methods:

Systematic review considering specific descriptors (children and adolescents, gastroesophageal reflux disease and multichannel intraluminal impedance-pH) and their synonyms. The systematic search was carried out in the MEDLINE/Ovid, Scopus, and Embase databases, considering the period from October 2017 to December 2018. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), which was used for study selection. The psychometric properties described in the studies were: sensitivity, specificity, accuracy, and reproducibility.

Results:

Sensitivity was discussed in most studies, with a result of more than 70% in four of them. Specificity was assessed only in conjunction with sensitivity, with values from 23% to 25% in two studies, and it reached 80% in a single study. Accuracy was assessed higher than 76% in one of the selected articles. The methodological quality of the studies demonstrated low risk of bias, and there was no significant concern related to applicability of the studies.

Conclusions:

According to the selected studies, multichannel intraluminal impedance-pH was considered a safe and effective tool, presenting higher sensitivity values than pHmetry regarding the diagnosis of gastroesophageal reflux disease.

KEYWORDS
Gastroesophageal reflux; Psychometric properties; Impedance pHmetry, pediatrics

Inclusion criteria	Exclusion criteria
Studies that used the MIIpH method for GERD diagnosis	Language other than English, Spanish, or Portuguese
Articles that evaluated at least one psychometric property	Studies that have not been published in full text format, abstracts, commentaries, editorials, meetings or presentations, proceedings from symposiums, seminars, round table discussions, debates, post scripts, letters to the editors, patents, case reports, reviews and systematic reviews, dissertations or theses, book chapters, and qualitative studies
Detailed description of the method used	Studies that evaluated the PP of only one isolated variable and not the MIIpH examination as a whole
Subjects evaluated between 0 and 20 years of age	Studies that included individuals between 0 and 20 years of age, but also included other ages

Study	Nationality	Design	Instruments	Population	N (sample)/ sex	Age years(y) or /months(m)	Psychometric property assessed MIIpH
Rosen et al., 2006¹⁶16 Rosen R, Lord C, Nurko S. The sensitivity of multichannel intraluminal impedance and the pH probe in the evaluation of gastroesophageal reflux in children. Clin Gastroenterol Hepatol. 2006;4:167-72.	United States	Prospective study and retrospective study	MIIpH	Children with recurrent respiratory and gastrointestinal symptoms	Total = 50	Untreated patients	Sensitivity
					Untreated patients (prospective) = 25 (14 M/11 F)	Mean age = 6.2 ± 5.3 y
					Treated patients (retrospectively MIIpH tracings) = 25 (16 M/9 F)	Treated patients
						Mean age = 7.2 ± 5.6 y
Dalby et al., 2007¹⁷17 Dalby K, Nielsen RG, Markoew S, Kruse-Andersen S, Husby S. Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pHmetry measurements in infants and children. Evaluation of a diagnostic procedure for gastroesophageal reflux disease. Dig Dis Sci. 2007;52:2159-65.	Denmark	Prospective study	Upper endoscopy	Infants and children with GERD symptoms	n = 30	Mean age = 4.7 y	Reproducibility
			MIIpH		Abnormal RI = 14
					Normal RI = 16
Misra, 2009¹⁸18 Misra S. Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study. J Gastroenterol Hepatol. 2010;25:817-22.	United States	Prospective observational cross-sectional study	MIIpH	Infants and children with suspected GER, with AS and without AS (NoAS) therapy	Total = 153 (95 AS; 58 NoAS)	Group 1 = 0-6 m	Sensitivity Specificity
					Group 1:	Group 2 = 6 m - 2 y
					Total = 61/NoAS = 18	Group 3 = 2-18 y
					Group 2:
					Total = 35/No AS = 12
					Group 3:
					Total = 57/NoAS = 28
					Sex = ND
Francavilla et al., 2010¹⁹19 Francavilla R, Magistà AM, Bucci N, Villirillo A, Boscarelli G, Mappa L, et al. Comparison of esophageal pH and multichannel intraluminal impedance testing in pediatric patients with suspected gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2010;50:154-60.	Italy	Prospectively study	MIIpH	Patients with suspected GERD	Total = 175 (112 M/63 F)	Mean age = 1.5y (0.2 m - 15.9 y)	Accuracy
					Infants < 12 m = 61	Infants = 7 m
					(36 M/25 F)	(0.2-1.8 m)
					Children >12 m = 114	Children = 4 y
					(76 M/38 F)	(1.2-5.9 y)
Blasco-Alonso et al., 2014²⁰20 Blasco-Alonso J, Yun-Castilla C, Girón-Fernández-Crehuet F, Peláez-Cantero MJ, Serrano-Nieto J, Navas-López VM, et al. Esophageal multichannel intraluminal impedance and pH-testing in the study of apparent life threatening episode incidents in infants. Rev Esp Enferm Dig. 2014;106:159-64.	Spain	Retrospective study	MIIpH and pHmetry	Infants < 1 year old with apparent life threatening episode (s)	Total = 39	Mean age = 3.52 m	Sensitivity Specificity
					(25 M/14 F)
Lau et al., 2016²¹21 Lau CT, Carlile AG, Wong KK, Tam P. The feasibility and efficacy of multi-channel intraluminal impedance monitoring in children. Pediatr Surg Int. 2016;32:119-23.	China	Retrospective study	MIIpH	Patients with aspiration pneumonia, GER symptoms, previous gastrostomy	Total = 34	69 m = (6-216 m)	Sensitivity
					(20 M/14 F)
Kızılkan et al., 2016²²22 Kizilkan NU, Bozkurt MF, Saltik Temizel IN, Demir H, Yüce A, Caner B, et al. Comparison of multichannel intraluminal impedance-pH monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux. World J Gastroenterol. 2016;22:9595-603.	Turkey	Prospective cross-sectional study	MIIpH, pHmetry, MII and GER scintigraphy (GES)	Children with suspected GERD	Total = 60	M = (8.7 ± 3.7 y)	Sensitivity Specificity
					(34 M/26 F)
Abdallah et al., 2017²³23 Abdallah A, El-Desoky T, Fathi K, Fawzi Elkashef W, Zaki A. Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring. Arab J Gastroenterol. 2017;18:68-73.	Egypt	Prospective cohort study	MIIpH and Bronchoalveolar lavage (BAL)	Wheezy infants	Total = 38	MIIpH abnormal = 7.6 ± 2 m	Sensitivity Specificity
					MIIpH abnormal = 23	MIIpH normal = 7.8 ± 2.3 m
					(15 M/8 F)
					MIIpH normal = 15
					(10 M/5 F)

Study	Objective	Psychometric property assessed MIIpH results	Conclusion
Rosen et al., 2006¹⁶16 Rosen R, Lord C, Nurko S. The sensitivity of multichannel intraluminal impedance and the pH probe in the evaluation of gastroesophageal reflux in children. Clin Gastroenterol Hepatol. 2006;4:167-72.	1.To determine the sensitivity of MII compared to the gold standard: pHmetry. (prospective study) and determine the importance of the episodes recorded only in the pHmetry in the interpretation of MII studies. 2.To review retrospectively MIIpH tracings to determine whether the sensitivity of pHmetry. Probe and MII differed while taking acid suppression therapy.	MIIpH = sensitivity: Untreated = 76.1% ± 13.5% Treated = 80.3 ± 21.2% MIIpH = Sensitivity calculated by age group 0-2 y = 80.4% ± 17.3% 2-10 = 80.8% ± 11.1% >10 y = 71.8% ± 25.5%	The sensitivity of MIIpH is superior to pHmetry in treated patients and similar in untreated patients. pHmetry-only episodes (episodes recorded only in pHmetry) might be important in the analysis of MIIpH studies and should not be excluded from the analysis until outcome studies are performed.
Dalby et al., 2007¹⁷17 Dalby K, Nielsen RG, Markoew S, Kruse-Andersen S, Husby S. Reproducibility of 24-hour combined multiple intraluminal impedance (MII) and pHmetry measurements in infants and children. Evaluation of a diagnostic procedure for gastroesophageal reflux disease. Dig Dis Sci. 2007;52:2159-65.	To investigate the reproducibility of reflux parameter obtained by two moments (24 h consecutive MIIpH) and the inter- and intraobserver variability of interpretation of combined MIIpH traces.	MIIpH reproducibility: All reflux episodes: LOA = 0.3-3.3 Acid reflux: LOA = 0.2-5.3 Non-acid: LOA = 0.5-1.5 Inter- and Intraobserver variability LOA = 0.5-1.5	Simultaneous MII and pHmetry monitoring is conveniently performed in children and infants, and MIIpH proved to be technically reliable. The less short variability found for acidic reflux episodes must be taken into consideration for the use of MIIpH in the clinical evaluation of infants and children with GERD.
Misra, 2009¹⁸18 Misra S. Can acid (pH) refluxes predict multichannel intraluminal impedance refluxes? A correlation study. J Gastroenterol Hepatol. 2010;25:817-22.	Explore if and when acid pH refluxes can predict refluxes detected by MII and verify if this correlation may indicate whether pHmetry and MIIpH are interchangeable.	RGE = RI ≥ 5% in simultaneous pHmetry. and MIIpH and RI ≤ 5% as 'negative' to RGE	The pHmetry in patients without acid suppression may reflect both acid and volume reflux activities verified by MII and can substitute for MIIpH for extra esophageal symptoms.
		ROC curves (No AS): MII indices (liquid, liquid with proximal migration, mixed, and mixed with proximal migration) = statistically significant	The correlation between acid and MII refluxes with proximal migration may justify using pHmetry for extra esophageal symptoms in patients without acid suppression.
		ROC curves (No AS and AS): MII indices (liquid and liquid with proximal migration) were statistically significant; modest areas under the curve (0.67 and 0.617, respectively)	In patients on acid suppression therapy MIIpH may be a better tool.
Francavilla et al., 2010¹⁹19 Francavilla R, Magistà AM, Bucci N, Villirillo A, Boscarelli G, Mappa L, et al. Comparison of esophageal pH and multichannel intraluminal impedance testing in pediatric patients with suspected gastroesophageal reflux. J Pediatr Gastroenterol Nutr. 2010;50:154-60.	Evaluate the diagnostic accuracy of MIIpH as compared with conventional pHmetry in detecting reflux events and symptom association in different age groups	MIIpH accuracy in detecting all reflux events: Mean (standard deviation), (confidence interval 95%):	MIIpH represents a powerful first-line test for the assessment of GERD.
		- Total = 86% (12%), (83-90)	The addition of impedance to conventional pHmetry significantly increase the diagnostic yield in detecting reflux events, prevalently in infants, and in revealing an association between refluxes and symptoms, prevalently respiratory ones and in the infants group.
		- Infants = 92% (8%), (88-95)
		- Children = 82% (13%), (77-88)
		MIIpH accuracy in detecting acid reflux events: mean (standard deviation), (95% confidence interval):
		- Total = 79% (15%), (74-84)
		- Infants = 83% (15%), (76-91)
		- Children = 76% (15%), (69-82)
Blasco-Alonso et al., 2014²⁰20 Blasco-Alonso J, Yun-Castilla C, Girón-Fernández-Crehuet F, Peláez-Cantero MJ, Serrano-Nieto J, Navas-López VM, et al. Esophageal multichannel intraluminal impedance and pH-testing in the study of apparent life threatening episode incidents in infants. Rev Esp Enferm Dig. 2014;106:159-64.	1.Describe the epidemiological and clinical data from infants admitted for ALTE. 2.Compare the results obtained via MIIpH and pHmetry determining the sensitivity and the specificity of each one.	MIIpH = 100% sensitivity/ 25%, specificity for the diagnosis of GERD in comparison to pHmetry	MIIpH is an essential technique for the diagnosis of GER in infants admitted for ALTE. The association of pHmetry and MII provides additional information that improves GER diagnosis.
Lau et al., 2016²¹21 Lau CT, Carlile AG, Wong KK, Tam P. The feasibility and efficacy of multi-channel intraluminal impedance monitoring in children. Pediatr Surg Int. 2016;32:119-23.	Review the early experience of MIIpH application in children.	MIIpH = 73.0% sensitivity in relation to pHmetry	MIIpH monitoring can be safely and effectively performed in pediatric patients. MIIpH appears to be more sensitive than conventional pHmetry.
Kızılkan et al., 2016²²22 Kizilkan NU, Bozkurt MF, Saltik Temizel IN, Demir H, Yüce A, Caner B, et al. Comparison of multichannel intraluminal impedance-pH monitoring and reflux scintigraphy in pediatric patients with suspected gastroesophageal reflux. World J Gastroenterol. 2016;22:9595-603.	1. Evaluate the agreement between MIIpH and GES for the diagnosis of GERD.	MIIpH = 87.2% sensitivity/ 23.1% specificity for the diagnosis of GERD in relation to GES	The most sensitive test for diagnosing GERD is MIIpH.
	2. Investigate the specificity of MIIpH and GES alone and compared with each other for diagnosis of GERD.		No or slight agreement was found between pHmetry, MII, MIIpH and GES for diagnosis of GERD.
Abdallah et al., 2017²³23 Abdallah A, El-Desoky T, Fathi K, Fawzi Elkashef W, Zaki A. Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring. Arab J Gastroenterol. 2017;18:68-73.	1. Determine the GERD prevalence using MIIpH versus pHmetry.	MIIpH = 77% sensitivity/80% specificity for the diagnosis of GERD related aspiration	MIIpH is superior to pHmetry in reflux-associated infantile wheeze diagnosis.
	2. Evaluate the sensitivity and specificity of objective MIIpH parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index.

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[1] ∗ Corresponding author. emiliasgoncalves@yahoo.com.br dirceu.unicamp@gmail.com (E.S. Gonçalves).