Incredible Review of GERD, BRUE, Aspiration, and Gastroparesis

Recently, Rachel Rosen gave a terrific review of reflux and reflux-related entities as part of our annual William (Billy) Meyers lectureship.  This lecture information would be helpful for every pediatric gastroenterologist as well as every pediatrician, pediatric ENT, pediatric pulmonologist, pediatric SLP and lactation specialist.  It puts to rest many obsolete ideas about reflux and its management. Some of her points have been covered by this blog previously (see links below) and by her bowel sounds podcast (see link below).   Some errors of omission and transcription may have occurred as I took notes during this lecture. 

Main points:

Reflux

  1. Using the label “GERD” increases the likelihood that an infant will be prescribed acid blockers; this phenomenon is noted as well with SLP and lactation specialist team members.  Everyone needs to be careful about ascribing infant symptoms to “reflux disease”
  2. AR formulas need acid to increase their viscosity (don’t use PPIs in infants taking AR formulas). Also, AR formula viscosity is hindered when mixed with breastmilk (don’t mix with breastmilk)
  3. Most infants with reflux have nonacid reflux.  PPIs do not help nonacid reflux
  4. PPIs are associated with increased aspiration and infection risks.  Acid suppression has been associated with increased risk of allergic diseases
  5. Rumination can look a lot like reflux on pH probe studies
  6. Reflux hypersensitivity, and functional heartburn can result in similar symptoms as reflux (can be distinguished with pH testing)
  7. Pepsin can increase lung inflammation and can be increased by PPI use
  8. Red airway appearance is NOT indicative of reflux (poor specificity, poor sensitivity)
  9. If having symptoms with transpyloric feedings, this indicates that the symptoms are NOT due to reflux; transpyloritc feedings have similar efficacy as a fundoplication
  10. Avoid fundoplication.  It does not result in fewer hospitalizations or improve pulmonary outcomes.  It can result in a number of complications
  11. Consider genotyping for CYP2C19 pharmacogenetics in patients receiving chronic PPI.  Those with rapid metabolism could benefit from higher doses.  Those with slow metabolism could benefit from lower doses.  Higher doses of PPIs increase risk for infections
  12. Bolus feedings result in fewer problems than continuous feedings

Delayed Gastric Emptying (Gastroparesis)

  1. Delayed GE is associated with increased lung bile acids.  This is important in lung transplant recipients and increased lung bile acids is seen more commonly in those with frequent admissions for respiratory issues
  2. In Dr. Rosen’s experience, prucalopride is currently the most useful promotility agent in documented gastroparesis

BRUE:

  1.  Infants with BRUE need to be tested for aspiration, not prescribed PPIs.
  2.  VSS (aka OPMS) has the highest yield of any test in infants with BRUE (~72% abnormal testing in one study). 
  3. Silent aspiration is common -don’t rely on SLP bedside assessment.
  4. Even with this diagnosis, many infants are still prescribed PPIs which increase the risk of complications (more hospitalizations, more infections, possible increase in allergies)

Aspiration:

  1. There are a number of potential etiologies, though most infants have aspiration due to neurological reasons (most transitory and improved by 7 months of age)
  2. In Boston, less than 5% with aspiration on VSS required GT placement
  3. Thickeners can be very helpful.  Practitioners need to know the differences (don’t use Simply Thick in 1st year of life due to NEC risk)

Chronic Cough:

  1. ~10% of kids with chronic cough have eosinophilic esophagitis (who have seen GI in Boston)

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Cacti at Tucson Botanical Gardens

Acid Suppression for Laryngomalacia -Handed This Article to My ENT Colleagues

DR Duncan et al. J Pediatr 2021; 238: 42-49. Acid Suppression Does Not Improve Laryngomalacia Outcomes but Treatment for Oropharyngeal Dysphagia Might Be Protective

This retrospective cohort study with 236 subjects (55% received acid blockers) provides a compelling argument that acid suppression is unlikely to be beneficial in infants with laryngomalacia and to consider the possibility of aspiration in them as well. Among all subjects, 27% received H2RA, 11% received PPI, and 17% received both.

Key findings:

  • Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates
  • Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment.
  • Subjects with moderate-to-severe laryngomalacia were more likely to have aspiration on a video fluoroscopic swallow study (VFSS)
  • Of the 40 patients who had a supraglottoplasty, only 4 (10%) had a VFSS before and afterwards. All repeat VFSS showed improvement at a mean of 4.7 months after supraglottoplasty

It is noted that 36% of subjects underwent a VFSS and 40% had a clinical feeding evaluation. The authors note that other studies have found “a high rate of silent aspiration in laryngomalacia.”

My take:

  1. Acid blockers are unlikely to be beneficial in infants with laryngomalacia and are potentially detrimental (findings limited by retrospective design in a tertiary care setting)
  2. Symptoms in children with laryngomalacia may be due to aspiration and evaluation is needed in those with significant symptoms

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WSJ 1/2/22: Why Cloth Masks Might Not Be Enough as Omicron Spreads

Reducing Gastrostomy Tube Placement in Children with Aspiration & COVID-19 Tracking

From The COVID Tracking Project: Effective Reproduction Number

These are up-to-date values for Rt, a key measure of how fast the virus is growing. It’s the average number of people who become infected by an infectious person. If Rt is above 1.0, the virus will spread quickly. When Rt is below 1.0, the virus will stop spreading.  All 50 states listed below (but hard to see) -these numbers adjust for testing frequency:

The site has each state -here are Georgia and Florida:


A recent study (McSweeney M, Meleedy-Rey P, Kerr J, Yuen JC, Fourneir G, Norris K, Larson K, Rosen R. A quality improvement initiative to reduce gastrostomy tube placement in aspirating patients. Pediatrics. 2020, 145: e20190325; DOI: https://doi.org/10.1542/peds.2019-0325) was highlighted by John Pohl in Practical Gastroenterology:

Full text summary: Reducing Gastrostomy Placement in Children with Aspiration

An excerpt:

Children equal to or less than 2 years of age with aspiration demonstrated on VFSS were included in the study…If a VFSS was abnormal and the child was less than 52 weeks gestational age, then the child either was admitted to the hospital for a trial of nasogastric (NG) breastmilk or oral thickened formula with NG breast milk. The patient then continued to work with SLP… If a repeat VFSS showed improvement in the swallowing mechanism, then work with SLP and trialing with thickened feeds continued until the aspiration had resolved as demonstrated by VFSS. However, if a repeat VFSS still showed aspiration, a child was considered a candidate for gastrostomy placement…

In total, 6125 patients at 2 years of age or less underwent a VFSS during the 4-year study period, and 1668 of these patients had aspiration or penetration… 94 of the patients with aspiration or aspiration and penetration on their first VFSS (12.2%) and 31 of the patients with penetration only on their first VFSS (3.4%) eventually required gastrostomy placement…

Gastrostomy placement in this patient population fell from 10.9% at the beginning of the study to 5.2% at the end…

The number of emergency room visits and hospitalizations in the patient group without gastrostomies did not increase during the study with this same patient group having significantly less emergency room visits and hospitalizations compared to those children who had undergone gastrostomy placement

My take: This study shows that conservative therapy allows most children (<2 yrs) to avoid gastrostomy tube placement

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My Favorite Posts from the Past Year

Recently, I listed the posts that had the most views in the past year –some dating back to 2012.  The following list includes less viewed but some of my favorite posts from 2018:

GI:

Nutrition:

LIVER:

Miscellaneous:

Flowers in Calgary

Clinical Evaluation Not Sensitive for Aspiration

A recent retrospective study (in press): abstract link: Presenting Signs and Symptoms do not Predict Aspiration Risk in Children DR Duncan et al. J Pediatr 2018;  https://doi.org/10.1016/j.jpeds.2018.05.030

From Boston Children’s Hospital Notes (9/12/18):

  • More than 80 percent of aspiration was silent
  • Rosen, Duncan and colleagues also found that observed feedings, even by very skilled clinicians, are not sensitive enough to diagnose aspiration in children because of the high rates of silent aspiration. Based on statistical analyses, the degree of agreement between observed feeding and the VFSS was poor for the diagnosis of aspiration.
  • Almost a third of the patients experienced symptoms during or after meals, which may help explain why physicians frequently misdiagnose oropharyngeal dysphagia with aspiration as gastroesophageal reflux disease (GERD).

Full abstract:

Objectives

To determine if any presenting symptoms are associated with aspiration risk, and to evaluate the reliability of clinical feeding evaluation (CFE) in diagnosing aspiration compared with videofluoroscopic swallow study (VFSS).

Study design

We retrospectively reviewed records of children under 2 years of age who had evaluation for oropharyngeal dysphagia by CFE and VFSS at Boston Children’s Hospital and compared presenting symptoms, symptom timing, and CFE and VFSS results. We investigated the relationship between symptom presence and aspiration using the Fisher exact test and stepwise logistic regression with adjustment for comorbidities. CFE and VFSS results were compared using the McNemar test. Intervals from CFE to VFSS were compared using the Student ttest.

Results

A total of 412 subjects with mean (±SD) age 8.9 ± 6.9 months were evaluated. No symptom, including timing relative to meals, predicted aspiration on VFSS. This lack of association between symptoms and VFSS results persisted even in the adjusted multivariate model. The sensitivity of CFE for predicting aspiration by VFSS was 44%. Patients with a reassuring CFE waited 28.2 ± 8.5 days longer for confirmatory VFSS compared with those with a concerning CFE (P < .05).

Conclusions

Presenting symptoms are varied in patients with aspiration and cannot be relied upon to determine which patients have aspiration on VFSS. The CFE does not have the sensitivity to consistently diagnose aspiration so a VFSS should be performed in persistently symptomatic patients.

My take: This study provides more data indicating that clinical evaluations are not reliable in children less than 2 years of age to exclude formal swallow study evaluations and that some symptoms attributed to reflux are in fact due to aspiration.

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Briefly noted: Mongersen, Aprepitant, and Anesthetic Outcomes

BG Feagan et al. Gastroenterol 2018; 154: 61-4.  In this study of GED-0301 (Mongersen), an antisense oligodeoxynucleotide affecting Smad7, was randomly assigned to 63 patients with Crohn’s disease (160 mg/day).  Endoscopic improvement was observed in 37%  at week 12. Clinical remission (CDAI<150) was noted in  32% (4 weeks of Rx), 35%  (8 weeks of Rx) and 48% (12 weeks of Rx). No new safety signals were noted.

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PJ Pasricha et al. Gastroenterol 2018; 154: 65-76.  First of all, I have to say that I like the visual abstracts in many Gastro studies.  In this randomized, double-masked “APRON” study of 126 patients with chronic nausea or gastroparesis receiving Aprepitant, a neurokinin-1 receptor antagonist, or placebo, the key findings were the following:

  • Aprepitant did not reduce symptoms of nausea significantly compared to placebo
  • Apreptiant-treated patients had improvements in secondary outcomes of symptom severity for nausea (1.8 vs 1.0, P=.005 on Gastroparesis Clinical Symptom Index) and overall symptoms (1.3 vs. 0.7, P=.001)

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B Bielawska et al. Gastroenterol 2018; 154: 77-85. Using data (administrative databases) and propensity matching from more than 3 million outpatient colonoscopies (2005-2012), the authors noted that the use of anesthesia assistance (AA) was associated with an increased risk of aspiration pneumonia (OR 1.63) but not perforation (OR 0.99). Though this study is limited by its retrospective design and reliance on administrative data, the authors state “the potential for residual confounding by indication for AA [is] extremely unlikely, especially because AA use in Ontario appears to be driven by institutional policy or business model rather than by patient factors.”

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Bright Angel Trail

#NASPGHAN 17 More Abstracts

This link for the NASPGHAN abstracts :NASPGHAN 2017 Scientific Abstracts

The following slides are from some of the abstract posters. This first poster (next 5 pics) showed that symptom association with meals is not predictive of aspiration among a selected group of children who underwent swallow study evaluations. In the figures, the blue bars are children who passed the swallow study whereas the red bars indicate the children who failed the swallow study.

This next slide demonstrated that a six food diet for EoE could be administered blenderized via a gastrostomy tube.

The next slide showed that irritable bowel syndrome was more frequent (overall hazard ratio of 1.52) following a urinary tract infection in the first year of life.

The next pictures are from a poster discussing high rates of recurrent C difficile infection following fecal microbial transplantation in pediatric patients with inflammatory bowel disease (mainly ulcerative colitis).  An inference from this study would be that many cases of C difficile that were attributed as causing symptoms could in fact have been from a flare up of their IBD.  More details about the diagnosis of C difficile (based on PCR or ELISA) would be helpful

The next poster provides data from CHOP experience with Ustekinumab.  Overall, in this highly-selected (refrcactory) population the long term improvement was low; while one-third had steroid-free remission at week 8, this was not maintained at week 16 and week 24.  In addition, among the 22 patients, one developed transverse myelitis.

This study that follows (next two pics) documented the relative safety of liver biopsies (mainly percutaneous without interventional radiology) in the post-transplant period.  The two most serious adverse events, cholangitis and bile leak, helped identify biliary strictures.

The following collaborative study examined the neurocognitive status of children with Alagille syndrome.  Overall, this study shows that children with Alagille syndrome are at increased risk of low IQ compared to children with other cholestatic diseases.

 

 

Does Reflux Lead to Increased Aspiration Pneumonia?

This post’s title question turns out to be quite tricky.  According to a recent study (RL Rosen et al. JPGN 2016; 63: 210-17), reflux burden, even in children that aspirate did not correlate with increased hospitalization.

Here are the details:

Methods: Prospectively recruited cohort of 116 children who had both pH-impedance testing along with modified barium swallow. The authors considered pathologic reflux to have at least 73 episodes on pH-impedance or if pH<4 for >6% of study period.

Key findings:

  • There was no statistical correlation between pH-impedance study results and total number of admissions even with or without adjusting for aspiration status (and neurologic complications).

When the authors tried to reconcile these findings, they offered three competing potential explanations for these results:

  • Reflux has little impact on hospitalziations
  • Our methods for measuring reflux are not good
  • Even “normal” reflux can be a problem for those prone to complications; therefore, reflux burden is not consequential.

What is clear is that pH-impedance studies cannot predict which patients are at risk for increased complications.  This is supported by data showing that ‘reflux-related’ hospitalizations may not improve after fundoplication (Pediatrics 2006; 118: 2326-33; J Pediatr Surg 2008; 43: 59-63).  One particularly important limitation was that the cause of hospitalizations was determined by medical record review.

My take: A simple algorithm for preventing aspiration pneumonia does not exist.  Even the role of reflux testing is uncertain.

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The accompanying article guaranteed that the pizza would pass through the body within 30 minutes.

The accompanying article guaranteed that the pizza would pass through the body within 30 minutes!!!

 

Which kids who aspirate need a gastrostomy tube?

While some may think all children who aspirate should have a gastrostomy tube, a recent study (ME McSweeney et al. J Pediatr 2016; 170: 79-84) indicates a more selective approach is appropriate.

This retrospective review of 114 patients (2006-2013) compared patients fed by gastrostomy tube (g-tube) and those who were fed orally.  In their introduction, the authors note, “there has been a practice shift at many institutions away from g-tube placement and more toward continuing to feed children with aspiration orally.”  All patients in the study had aspiration and/or penetration with thin liquids and/or nectar thick liquids on a videofluoroscopic swallow study (VFSS).

There were 61 who aspirated only thin liquids and 53 who aspirated thin and nectar thick liquids.  All patients were divided into two groups: a g-tube group which did not have a preoperative trial of thickened feeds and an orally-fed group.  Patients who had a fundoplication or post-pyloric feeds were excluded from this study.

Key findings:

  • There were no significant differences in admissions among those who aspirated thins compared with those that aspirated thin & nectar thick liquids.
  • Patients fed by gastrostomy were hospitalized more frequently (median 2 times compared to once with orally-fed) and for longer duration (median 24 days compared with median 2 days for orally-fed)
  • No differences in total pulmonary admissions were noted between gastrostomy-fed and orally-fed group

The authors advocate a trial of oral feeding in all children cleared to take nectar or honey thick liquids prior to g-tube placement.

 

While the authors note that g-tube placement did not result in fewer pulmonary admissions, in their discussion, they also reviewed studies which showed that fundoplication (with g-tube) was not associated with a reduced risk of respiratory complications and in fact, had higher rehospitalizations.

This current study, and previous studies, are limited by their design.  Patients were not randomized and g-tube-fed patients may have had more comorbidities, biasing the results.  The authors note that there were 11 children who failed oral thickening trials and needed g-tube placement.  At the same time, there are substantial numbers of children whose swallow function improve.  Also, the authors note that thickening agents have not been shown to lead to dehydration risk.

My take: the widespread availability of swallow studies has likely led to some children undergoing g-tube placement who may have been fine with ongoing orally-thickened feeds.  Avoiding g-tube placement for children who can tolerate and thrive on thickened feeds is worthwhile.

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Walnut Street Bridge & Tennessee River

Walnut Street Bridge & Tennessee River

Antibiotics and Growth in India

A recent study (Rogawski ET, et al. J Pediatr 2015; 167: 1096-102) examined a prospective observational cohort of 497 children in India (from “semi-urban slums”).  The authors found that early exposure to antibiotics were not associated with increased or decreased growth.

“There are several potential explanations for the lack of a growth-promoting effect.  Most of the previous studies showing increased weight gain or risk of obesity associated with antibiotics were conducted in high-income countries with Western diets.”

My take: This was a negative study on antibiotics and obesity.  This suggests that the effects of antibiotics with regard to weight gain may be limited and/or modified by diet.

Also noted: Wakamoto H, et al. J Pediatr 2015; 167: 1136-42.  This study showed that Krebs von den Lungen-6 (KL-6) which is abundant on type II alveolar pneumoctyes and respiratory epithelial cells is a fairly good serum biomarker for chronic aspiration in this study of children with severe motor and intellectual disabilities.  Figure 1 shows the distribution of KL-6 among the 37 with aspiration and the 29 without aspiration.  The median in the former was 344 vs 207 in the later, though there was overlapping results.

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Sandy Springs

Sandy Springs