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Successful multichannel intraluminal impedance and pH monitoring (MII-pHM) studies rely on constant attendants (CAs) or family members (and sometimes the patients themselves) to assist in the execution and facilitation of the MII-pHM study. While "pushing buttons" [corresponding to specific symptoms, body position (upright versus recumbent), and meal start and stop times] on the MII-pHM system recording box is indeed a big part of MII-pHM study execution and facilitation, there are other concerns and duties that are equally as important. This paper outlines some of the important duties of the study facilitator (or patient) during a MII-pHM study. When provided with the proper training, study facilitators invigilating the MII-pHM study will be better able to contribute to the data collection process and ultimately to produce data that when analyzed will lead to better interpretations, clinical recommendations, and good clinical outcomes. When executed properly, MII-pHM studies have the potential to assess diurnal exposure of the esophageal mucosa to gastric/duodenal contents, provide insight regarding the proximal extent of gastroesophageal reflux (GER), provide a measurement of the mean esophageal pH, and assess mucosal integrity and temporal relationship between GER and the symptoms of interest. While several groups have offered recommendations for proper execution of the MII-pHM study, to our knowledge, there have not been publications wherein recommendations were compiled to form a single source document., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tgh.amegroups.com/article/view/10.21037/tgh-23-119/coif). The authors have no conflicts of interest to declare., (2024 Translational Gastroenterology and Hepatology. All rights reserved.)

Background/aims: To assess the effectiveness and feasibility of a brief session of hypnosis to reduce distress in children with functional constipation undergoing anorectal manometry (ARM)., Methods: A partially-blinded randomized controlled pilot trial was conducted in children 4-18 years old scheduled for ARM. Children were randomized to receive a brief session of hypnosis prior to ARM or standard care. Non-blinded and blinded observers rated the child's level of distress using the Observation Scale of Behavioral Distress and a 4-point-Likert scale, respectively. Differences between groups were analyzed using Fisher's exact test or Mann-Whitney U test as appropriate., Results: Data from 32 children (15 hypnosis and 17 standard care) were analyzed. Prior to insertion of the catheter, the observed mean levels of distress were lower in the hypnosis group according to both the non-blinded observer (median 0.0 [interquartile range {IQR} 0.0-0.3] vs 1.4 [IQR 0.3-2.4]; P = 0.009) and the blinded observer (median 0.0 [IQR 0.0-0.0] vs 0.5 [IQR 0.0-1.0]; P = 0.044). During ARM, observed and reported levels of distress did not differ significantly. In the hypnosis group, 92.9% of parents and children reported that hypnosis helped the child to relax. There were no significant differences in resting pressure, squeeze pressure, or duration of the procedure between both groups., Conclusion: A brief session of hypnosis for children before ARM is an easily incorporable intervention that lowers distress levels prior to the procedure and is positively perceived by children and parents.

Background: People with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment., Research Question: We characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx., Study Design and Methods: PWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry., Results: Twenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not., Interpretation: Our findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

A few studies have shown that esophageal air events (EAEs), such as air-swallows, may be associated with symptoms that have historically been associated with gastroesophageal reflux disease (GERD). To objectively test a hypothesis that all EAE types (air-swallows, supragastric belches and gastric belches) can be associated with GERD-like symptoms, we removed the impedance "tags" from the GER episodes (placed during autoscan) and instead tagged either air-swallows, supragastric belches or gastric belches in each of 3 copies of the 24-hour impedance tracing for 2 infant patients who presented with symptoms suggestive of GER as an etiology. Impedance system software (MMS) analyses revealed that, in both infants, all EAE types were significantly associated (SAP >95%) with 1 or more of the GERD-like symptom types (cough, pain/crying, back-arching, and gagging). These data underscore the importance of considering other diagnoses when developing management strategies for treating GERD-like symptoms in infants.

Background: Scientific advances have improved longevity in cystic fibrosis (CF) patients and many of these patients can expect to experience age-related gastrointestinal co-morbidities. We aimed to assess the extent to which age might impact gastroesophageal reflux (GER) in patients with CF., Methods: Our esophageal pH-multichannel intraluminal impedance monitoring database was searched for tracings belonging to CF patients ≥2 years old without prior fundoplication and not taking anti-reflux medications immediately prior (within 7 days) and during the study. Tracings were retrospectively analyzed; Impedance and pH variables were evaluated with respect to age and pulmonary function., Results: Twenty-eight patients were enrolled; 16 children (3.1-17.7 years) and 12 adults (18.2-48.9 years). Among pH probe parameters, correlation analysis showed DeMeester score (P=0.011) and number of acid reflux events lasting >5 minutes (P=0.047) to be significantly correlated with age. Age was not significantly correlated with any of the impedance parameters. Age was negatively correlated with baseline impedance (BI) in the distal esophagus (r=-0.424, P=0.023) and BI was negatively correlated with several pH parameters, including reflux index (r=-0.553, P=0.002), number of total acid reflux events (r=-0.576, P=0.001), number of acid reflux events lasting >5 minutes (r=-0.534, P=0.003), and DeMeester score (r=-0.510, P=0.006). Pulmonary function (percent predicted forced expiratory volume in one minute; ppFEV 1 ) was negatively correlated with age (r=-0.494, P=0.0007). The interaction of age and ppFEV 1 and any of the reflux parameters, however, was not significant (P>0.05); the strongest evidence for an interaction was found for the number of acid reflux events reaching the proximal esophagus, but this interaction still did not reach statistical significance (P=0.070)., Conclusions: In a small cohort, we found evidence that age may be associated with increased acid exposure and that both age and increased acid exposure are associated with reduced BI in the distal esophagus. The negative relationship between pulmonary function and age in our cohort is not related to GER. This pilot study supports the need for esophageal assessment and treatment of GER as standard components of clinical care for an aging CF population., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Translational Gastroenterology and Hepatology. All rights reserved.)

Background: Mechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe's impact on inflammation mediators and infection in children with CF., Methods: Seventy-seven children with CF <10 years of age ( 35 infants <1 year; 42 children 1-10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed., Results: Hair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D 2 (PGD 2 ) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD 2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages., Conclusions: Infants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Gastroesophageal reflux (GER) is the retrograde movement of gastric (and sometimes duodenal) contents into the esophagus. While the majority of GER is physiologic, for patients, it can be associated with symptoms. While some symptoms are merely bothersome (crying), others can be life threatening (cough, gagging, choking). The main driver of GER in infants is the frequent feedings that produce increased intra-abdominal pressure, which is known to trigger transient relaxations of the lower esophageal sphincter. The recent 2018 clinical practice guidelines reported by the North American and European Societies for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN/ESPGHAN) have recommended non-pharmacologic management initially with subsequent consideration of brief trials with acid suppressants. The main target for these acid suppressants is the gastric parietal cells. Our review of the literature has revealed a paucity of data regarding the use of histamine-2 receptor antagonists and proton pump inhibitors in infants. Despite the absence of well-controlled clinical studies, the prescription rate of these medications has increased internationally. Risks to patients of all ages have become increasingly recognized, with new associations being reported all too often. Here we report our review of all pharmacologic modalities as well as some non-surgical options.

Background: Cystic fibrosis (CF) is a life-limiting disease caused by a defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Lumacaftor/Ivacaftor is a novel CFTR modulator approved for patients that are homozygous for Phe508del CFTR, but its clinical effectiveness varies amongst patients, making it difficult to determine clinical responders. Therefore, identifying biochemical biomarkers associated with drug response are clinically important for follow-up studies., Methods: Serum metabolomics was performed on twenty patients with CF pre- and 6-month post-Lumacaftor/Ivacaftor response via Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectroscopy (UPLC-MS/MS). Correlation with clinical variables was performed., Results: Metabolomics analysis demonstrated 188 differentially regulated metabolites between patients pre- and post-Lumacaftor/Ivacaftor initiation, with a predominance of lipid and amino acid alterations. The top 30 metabolites were able to differentiate pre- and post-Lumacaftor/Ivacaftor status in greater than 90% of patients via a random-forest confusion matrix. Alterations in bile acids, phospholipids, and bacteria-associated metabolites were the predominant changes associated with drug response. Importantly, changes in metabolic patterns were associated with clinical responders., Conclusions: Selected key lipid and amino acid metabolic pathways were significantly affected by Lumacaftor/Ivacaftor initiation and similar pathways were affected in clinical responders. Targeted metabolomics may provide useful and relevant biomarkers of CFTR modulator responses., (© 2018 Wiley Periodicals, Inc.)

Purpose: Acid neutralization during chemical clearance is significantly prolonged in children with cystic fibrosis, compared to symptomatic children without cystic fibrosis. The absence of available reference values impeded identification of abnormal findings within individual patients with and without cystic fibrosis. The present study aimed to test the hypothesis that significantly more children with cystic fibrosis have acid neutralization durations during chemical clearance that fall outside the physiological range., Methods: Published reference value for acid neutralization duration during chemical clearance (determined using combined impedance/pH monitoring) was used to assess esophageal acid neutralization efficiency during chemical clearance in 16 children with cystic fibrosis (3 to <18 years) and 16 age-matched children without cystic fibrosis., Results: Duration of acid neutralization during chemical clearance exceeded the upper end of the physiological range in 9 of 16 (56.3%) children with and in 3 of 16 (18.8%) children without cystic fibrosis ( p =0.0412). The likelihood ratio for duration indicated that children with cystic fibrosis are 2.1-times more likely to have abnormal acid neutralization during chemical clearance, and children with abnormal acid neutralization during chemical clearance are 1.5-times more likely to have cystic fibrosis., Conclusion: Significantly more (but not all) children with cystic fibrosis have abnormally prolonged esophageal clearance of acid. Children with cystic fibrosis are more likely to have abnormal acid neutralization during chemical clearance. Additional studies involving larger sample sizes are needed to address the importance of genotype, esophageal motility, composition and volume of saliva, and gastric acidity on acid neutralization efficiency in cystic fibrosis children.

To quantify and compare maximal extent (height) of acid reflux events (AREs) on symptom generation in dysphagic neonates. Dysphagic neonates (N = 53), born at 30 ± 5.3 weeks gestation, underwent 24-hour pH-impedance study for the evaluation of troublesome symptoms purported to be due to gastroesophageal reflux disease (GERD). AREs (pH < 4 for >4 s) detected by impedance (Z) were categorized by maximal extent as refluxate reaching distal (Z6, Z5), middle (Z4, Z3), or proximal (Z2, Z1) impedance channels. AREs reaching the pH sensor only were categorized as distal. Symptom correlation (%, symptom index, symptom sensitivity index, and symptom associated probability) and temporal characteristics (clearance times) of AREs were analyzed using linear mixed and GEE models comparing height categories presented as mean ± SEM, median (IQR), and OR (95% CI). Of the 2003 AREs, 1) distal extent AREs (n = 1642) had increased frequency (p < 0.05), decreased ACT (p < 0.05), and decreased acidity (p < 0.05); 2) in middle and proximal AREs, acid clearance was longer than bolus clearance, (p < 0.01); and 3) the odds of having cardiorespiratory (cough or sneeze) symptoms are increased with proximal and middle AREs (p < 0.05). Most proximal ascent of AREs into middle or proximal esophagus likely activates protective aerodigestive reflexes (peristalsis) or vigilant states to facilitate bolus and chemical clearance. Heightened esophageal sensitivity, acid neutralization delays, or clearance mechanism delays may accentuate multi-systemic troublesome symptoms.

Background: Survival in cystic fibrosis patients after liver transplantation and liver-lung transplantation is not well studied., Aims: To discern survival rates after liver transplantation and liver-lung transplantation in patients with and without cystic fibrosis., Methods: The United Network for Organ Sharing database was queried from 1987 to 2013. Univariate Cox proportional hazards, multivariate Cox models, and propensity score matching were performed., Results: Liver transplant and liver-lung transplant were performed in 212 and 53 patients with cystic fibrosis, respectively. Univariate Cox proportional hazards regression identified lower survival in cystic fibrosis after liver transplant compared to a reference non-cystic fibrosis liver transplant cohort (HR 1.248; 95 % CI 1.012, 1.541; p = 0.039). Supplementary analysis found graft survival was similar across the 3 recipient categories (log-rank test: χ(2) 2.68; p = 0.262). Multivariate Cox models identified increased mortality hazard among cystic fibrosis patients undergoing liver transplantation (HR 2.439; 95 % CI 1.709, 3.482; p < 0.001) and liver-lung transplantation (HR 2.753; 95 % CI 1.560, 4.861; p < 0.001). Propensity score matching of cystic fibrosis patients undergoing liver transplantation to non-cystic fibrosis controls identified a greater mortality hazard in the cystic fibrosis cohort using a Cox proportional hazards model stratified on matched pairs (HR 3.167; 95 % CI 1.265, 7.929, p = 0.014)., Conclusions: Liver transplantation in cystic fibrosis is associated with poorer long-term patient survival compared to non-cystic fibrosis patients, although the difference is not due to graft survival.

Purpose: This study was performed to evaluate the quality of sleep in snoring obese children without obstructive sleep apnea (OSA); and to study the possible relationship between sleep interruption and gastroesophageal reflux (GER) in snoring obese children., Methods: Study subjects included 13 snoring obese children who were referred to our sleep lab for possible sleep-disordered breathing. Patients underwent multichannel intraluminal impedance and esophageal pH monitoring with simultaneous polysomnography. Exclusion criteria included history of fundoplication, cystic fibrosis, and infants under the age of 2 years. Significant association between arousals and awakenings with previous reflux were defined by symptom-association probability using 2-minute intervals., Results: Sleep efficiency ranged from 67-97% (median 81%). A total of 111 reflux episodes (90% acidic) were detected during sleep, but there were more episodes per hour during awake periods after sleep onset than during sleep (median 2.3 vs. 0.6, p=0.04). There were 279 total awakenings during the sleep study; 56 (20.1%) of them in 9 patients (69.2%) were preceded by reflux episodes (55 acid, 1 non-acid). In 5 patients (38.5%), awakenings were significantly associated with reflux., Conclusion: The data suggest that acid GER causes sleep interruptions in obese children who have symptoms of snoring or restless sleep and without evidence of OSA.

Background: Survival in non-cystic fibrosis (CF) bronchiectasis is not well studied., Methods: The United Network for Organ Sharing database was queried from 1987 to 2013 to compare survival in adult patients with non-CF bronchiectasis to patients with CF listed for lung transplantation (LTx). Each subject was tracked from waitlist entry date until death or censoring to determine survival differences between the two groups., Results: Of 2112 listed lung transplant candidates with bronchiectasis (180 non-CF, 1932 CF), 1617 were used for univariate Cox and Kaplan-Meier survival function analysis, 1173 for multivariate Cox models, and 182 for matched-pairs analysis based on propensity scores. Compared to CF, patients with non-CF bronchiectasis had a significantly lower mortality by univariate Cox analysis (HR 0.565; 95 % CI 0.424, 0.754; p < 0.001). Adjusting for potential confounders, multivariate Cox models identified a significant reduction in risk for death associated with non-CF bronchiectasis who were lung transplant candidates (HR 0.684; 95 % CI 0.475, 0.985; p = 0.041). Results were consistent in multivariate models adjusting for pulmonary hypertension and forced expiratory volume in one second., Conclusions: Non-CF bronchiectasis with advanced lung disease was associated with significantly lower mortality hazard compared to CF bronchiectasis on the waitlist for LTx. Separate referral and listing criteria for LTx in non-CF and CF populations should be considered.

Background and Aim: We reported that chemical clearance (CC) of acid gastroesophageal reflux (AGER) is relatively prolonged in children with cystic fibrosis (CF). Disparity in CC values within our CF cohort sparked curiosity as to what CC looks like in infants and children with AGER in the physiologic range. The aim of the study was to assess CC in infants and children with normal AGER., Methods: Impedance-pH tracings from our database for infants (≤ 12 months) and children (>12 months-18 years) were manually scanned for 2-phase AGER episodes. Tracings were excluded for patients who had AGER Indices >3% (children) or >6% (infants), had positive GER-symptom associations, were on antireflux medications, had a fundoplication, or had impedance studies shorter than 18 hour. In addition to medians (25%-75% interquartile range), we calculated the 95th percentile for the CC duration and the fifth percentile for the CC rate., Results: Two-phase AGER episodes were detected in 44 infants and 60 children. The median CC duration was 64.3 seconds (51.0-91.6 seconds) for infants and 37.5 seconds (27.7-52.4 seconds) for children. The median CC rate was 0.0622 pH units/second (PU/second) (0.0354-0.0946 PU/second) for infants and 0.0928 PU/second (0.0631-0.2057 PU/second) for children. The CC duration at the 95th percentile was 148.5 seconds for infants and 114.4 seconds for children. The CC rate at the fifth percentile was 0.0088 PU/second for infants and 0.0465 PU/second for children., Conclusions: We report reference values for CC in infants and children who have normal acid reflux. These values should not be used as "cutoff values" because they were derived from infant and children cohorts that did not include individuals with intermediate AGER.

Although combined multichannel intraluminal impedance/esophageal pH monitoring (MII-pH) has replaced prolonged pH monitoring alone for assessing gastroesophageal reflux (GER) in the pediatric population, it does so in the absence of reference values for non-acid GER (NAGER). The purpose of this study was to identify a normal range of NAGER impedance values for infants and children. We evaluated EPM/MII tracings for patients referred for GER assessment to Nationwide Children's Hospital (Columbus, OH), Inova Children's Hospital, and Hospital Italiano (Buenos Aires, Argentina). We excluded tracings from patients who had AGER indices greater than 50 % of the upper end of normal (i.e., >3 % for children >12 months and >6 % for infants ≤ 12 months), had a positive temporal association of GER with symptoms, were on anti-reflux medications at the time of the study, and/or had a fundoplication prior to the study. We also excluded studies with durations shorter than 20 h. Values for NAGER percent time, NAGER episode frequency, frequency of proximal NAGER, and mean NAGER duration were calculated for upright position, recumbent, and total. Study population consisted of 46 infants (20 female [F]/26 male [M], median age 4.8 months [range 3 weeks-11.9 months]) with a median AGER index of 2.2 % (range 0.0-5.9 %) and 71 children (22 F/49 M, median age 7.2 years [range 1.3-17 years]) with a median AGER index of 1.1 % (range 0-3.0 %). Data are presented in tables in the text. The results of this study provide a range of values characteristic of infants and children with normal AGER indices and no positive temporal associations of GER with symptoms. These values may be used as references for comparison to identify infants and/or children who may be at risk of developing serious clinical manifestations due to abnormal patterns of GER.

Objectives: Few studies compare gastroesophageal reflux (GER) parameters of cystic fibrosis (CF) children and symptomatic non-CF children. We aimed to compare the impedance-pH (IMP-pH) parameters for these two groups and to test the hypothesis that prolonged acid exposure in CF patients is due to delayed chemical clearance (CC)., Methods: IMP-pH tracings from 16 CF children (median 8.2 years) and 16 symptomatic non-CF children (median 8.3 years) were analyzed. Software was used to generate IMP-pH reports and parameter data were extracted. IMP-pH was used to calculate the mean CC for each patient., Results: pH studies showed no difference in acid GER (AGER) frequency (p = 0.587); however, mean AGER duration, duration of longest AGER, AGER index, and DeMeester scores were all significantly higher for CF patients. IMP showed no difference in GER frequency [neither acidic (p = 0.918) nor non-acidic (p = 0.277)], but total bolus clearance was more efficient in CF patients (p = 0.049). A larger percentage of total GER reached the proximal esophagus in non-CF children (p = 0.039). Analyses of two-phase AGER episodes showed that these events were more acidic (p = 0.003) and the CC phase was significantly prolonged in the CF cohort (p = 0.001)., Conclusions: Compared to symptomatic non-CF children, CF children do not have more frequent reflux. Actually, they have better bolus clearance efficiency following reflux and may even have better control over the number of GER episodes that reach the proximal esophagus. CC of AGER, however, is significantly prolonged in the CF cohort, likely due to hyperacidity of refluxed gastric contents.

Background and Aim: Little is known about the relation between gastroesophageal reflux (GER) episodes and sleep interruptions in infants. The aim of the study was to evaluate the relationship between GER and the incidence of sleep interruptions in infants., Methods: Study patients included 24 infants (younger than 1 year) referred for multichannel intraluminal impedance and esophageal pH monitoring with simultaneous polysomnography. Exclusion criteria were a previous fundoplication and studies lasting <20 hours. Tests were clinically indicated to investigate suspicion of GER-related apnea (17, 70.8%), stridor (6, 25%), noisy breathing (2, 8.3%), and cyanotic spells (1, 4.2%). Most patients presented with significant comorbidities (19, 79.2%)., Results: The number of nonacid GER (NAGER) per hour was greater during sleep time than during daytime and awakening following sleep onset (median 0.27 vs 1.85 and 1.45, P<0.01). A total of 1204 (range 7-86 per infant) arousals in 24 infants was detected, 165 (13.7%) that followed GER episodes, and 43 (3.6%) that preceded GER episodes. Seven patients presented with a positive symptom association probability for arousals; 5 were exclusively because of NAGER. A positive symptom association probability for awakenings was detected in 9 patients; 4 were because of NAGER, 4 were because of AGER, and 1 was because of both NAGER and GER. Patients with awakenings related to GER presented longer mean clearance time of AGER during sleep (165.5 vs 92.8 seconds, P=0.03)., Conclusions: GER was a frequent cause of interrupting sleep among our infant patients, and NAGER proved to be equally important as AGER for causing arousals and awakenings in infants.

Cystic fibrosis (CF) is an inherited disease that affects both the lungs and the digestive system in children and adults. Thick mucus fills the gut and blocks lumens of the pancreas and hepatobiliary systems, creating insufficient pancreas function and liver disease. Chronic gastrointestinal (GI) complications, including intestinal obstruction, occur in neonates, and poor digestion and gastroesophageal reflux disease (GERD) in children. Although GI symptoms tend to improve with age, CF and associated GERD eventually create respiratory insufficiency; the only available treatment option at this stage is a bilateral lung transplant, which carries considerable morbidity and mortality. While GERD may reoccur as a complication of lung transplantation, GERD symptoms are often reduced following a fundoplication.

Background & Aims: Clearance of acid gastroesophageal reflux is biphasic. During volume clearance, refluxed material is cleared from the esophagus by peristalsis, and during chemical clearance, acidified esophageal mucosa is neutralized by saliva and possibly secretions from the esophageal lumen. In this study, we examined the effects of feeding on the durations of volume clearance and chemical clearance., Methods: Combined pH/multichannel intraluminal impedance tracings from 12 symptomatic infants (median age, 20 weeks) were analyzed. Acid gastroesophageal reflux episodes having both volume clearance and chemical clearance components were grouped into 1 of 4 feeding cycle phases (feeding, first hour postprandial, second hour postprandial, and fasting)., Results: Mean duration of volume clearance and chemical clearance was 7.0 +/- 2.3 and 36.3 +/- 8.5 minutes (P = .001), respectively, per patient and 24.7 +/- 2.7 and 127.5 +/- 10.7 seconds (P < .0001), respectively, per episode. Whereas volume clearance did not change throughout the feeding cycle, chemical clearance was significantly prolonged during fasting (132.2 +/- 18.4 seconds) compared with feeding (13.5 +/- 4.1 seconds, P = .0046) and 1st postprandial (64.0 +/- 19.4 seconds, P = .0333). Statistical analysis failed to demonstrate a significant relationship between nadir pH and chemical clearance (P = .3104) or between chemical clearance and the interaction between nadir pH and feeding cycle., Conclusions: Chemical clearance is significantly prolonged during fasting in infants. Falling pH alone cannot explain declining chemical clearance efficiency during later postprandial periods. We speculate that inefficient chemical clearance during fasting is likely due to reduced efficiency of acid clearance mechanisms that could include salivation, swallowing, peristalsis, and/or intraluminal secretion.

Twenty-four-hour tracings generated from combined esophageal pH and multichannel intraluminal impedance measurements of 14 infants (nine males, median age 3.5 months) were examined retrospectively. For each tracing, two acid reflux assessment reports were generated using either pH monitoring alone or pH monitoring combined with impedance. Significantly fewer acid reflux episodes were detected using pH monitoring combined with impedance when compared to pH monitoring alone (25.1+/-4.0 versus 99.9+/-18.3 episodes/patient, p=.001). Estimates of esophageal acid exposure using pH monitoring alone were two-fold higher (137.4+/-23.7 versus 66.6+/-15.9 min/patient, p=.002) than estimates derived using both techniques. Of the total acid reflux episodes detected by pH monitoring alone, 71.8% could not be confirmed by combined pH and impedance. Detection of significant numbers of "pH-only" episodes raises concerns regarding possible over-estimations of acid exposure that may occur when estimates are based solely on esophageal pH monitoring.

Background: There is controversy regarding the association between gastroesophageal reflux and apnea. The controversy is further confused by the variety of ways reflux is detected, the varying methods of data analysis and the heterogeneity of subjects studied., Objectives: To determine if apnea is associated with reflux and to determine whether the association differs with acid or non acid reflux., Methods: We prospectively evaluated infants with apparent life-threatening events or apnea by simultaneous pneumography, esophageal pH and multichannel intraluminal impedance monitoring. Apneic events and reflux frequency, duration, acidity and height were recorded. Apneic events were considered to be temporally linked to gastroesophageal reflux when they occurred during a gastroesophageal reflux episode or within 5 minutes after clearance of the refluxate. Data described with frequency tables, scatterplots and time series graphs were analyzed by regression analysis and chi testing., Results: Twenty-five infants (10 males) aged 1 to 19 months were studied for up to 24 hours. Of 527 total apneic episodes, only 80 (15.2%) were temporally linked with gastroesophageal reflux: 37 (7.0%) with acid reflux and 43 (8.2%) with non-acid reflux. Scatterplots revealed no significant correlation between apnea and frequency or duration of reflux episodes. Individual chi analyses within subjects found limited associations between reflux and apnea. Regression analyses showed a significant association between apnea and reflux in 4 of 25 subjects., Conclusions: We found little evidence for an association between apnea and total reflux, acid reflux or non-acid reflux. There was no difference between acid gastroesophageal reflux and non-acid gastroesophageal reflux in the frequency association with apnea. Either a chi statistic for each subject or R value computed from a lagged regression model for each subject can be used as an index of association in patient evaluation.