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Clinical Evaluation Not Sensitive for Aspiration

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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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Fecal Microbiota Transplantation: How important is the BMI of the stool donor?

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Currently fecal microbiota transplantation (FMT) “best practices” exclude obese stool donors based on a report of germ-free mice gaining weight after FMT from mice with obesity and based on a case report of an individual with 34 pound weight gain after FMT.

A recent report (M Fischer et al. Clin Gastroenterol Hepatol 2018; 16: 1351-3) suggests that the the BMI of the stool donor does not affect recipient weight after a single FMT procedure for C difficile infection.

This analysis included 173 patients with a mean age of 57 years.  One group of 103 were from a randomized control trial; in this group, 66 (64%) received FMT from a normal weight (BMI 18-24.9) donor and 37 (36%) received FMT from an overweight (BMI 25-29.9) donor. Among an additional 70 individuals from an observational cohort, 25 received FMT from normal weight donor, 30 received FMT from overweight donor, and 15 received FMT from an obese donor.

Key finding:

  • There was no significant difference in BMI among the FMT recipients up to 48 weeks after a single FMT.  Based on data from Figure 1, patients who received FMT from normal weight donor had slightly higher mean weight gain at 48 weeks afterwards (not statistically-significant)

The authors caution that a prospective study is required to confirm these findings and in the interim, they recommend exclusion of obese/overweight FMT donors.

My take: There are plenty of willing stool donors –so who knows if this will ever be examined adequately.  This study challenges the idea that FMT from an obese donor will result in recipient obesity, presumably via changes in the microbiome.

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Exclusive Enteral Nutrition for Crohn’s Disease -Less Effective in Those with Isolated Colonic Disease

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A recent study (Y Xu. Clinical Nutrition 2018; https://doi.org/10.1016/j.clnu.2018.08.022) showed that exclusive enteral nutrition (EEN) is less effective in patient’s with Crohn’s disease with isolated colonic disease.

Abstract Link: Isolated Colonic Crohn’s Disease is Associated with a Reduced Response to Exclusive Enteral Nutrition Compared to Ileal or Ileocolonic Disease

This was a retrospective study of 241 adults: 52 patients in the cCD (isolated colonic disease) group and 189 patients in the non-cCD group.

Key findings:

  • “The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2 –6.23], P = 0.016).”
  • “Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group.”

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Low Adherence Rate with Polyethylene Glycol

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The sentiment of wanting to get their kid off laxatives/stool softeners is frequently expressed at GI visits.  I certainly understand this.  Though, if a child is not stooling adequately when these medicines are withheld, this is usually detrimental for the child.

Given the frequency of this sentiment, it is not surprising that a recent study (IJN Koppen et al. J Pediatr 2018; 199: 132-9) reports low adherence with polyethylene glycol treatment in children with functional constipation.

In this cross-sectional survey using the Medication Adherence Report Scale (MARS-5), with scores of ≥23 indicating better adherence, the authors found that only 43 of 115 (37%) children were adherent.  The authors note that one of the determinants of adherence was treatment convenience.

The MARS-5 does not objectively measure the exact intake of medication; thus, the exact rate of adherence is unclear.  In addition, there is likely to wide variation in adherence among different populations.

My take: this study shows, at least in some populations, a low adherence with constipation therapy.  Sticking with treatment, for constipation and every other condition, usually results in better outcomes.

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If someone is not taking their medication, perhaps this cereal would help. (I am not officially endorsing this product, but think the name is funny.)

Transmural Disease, Biomarkers, and Correlation between MRI and Endoscopy

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A recent study (I Weinstein-Nakar et al. Clin Gastroenterol Hepatol 2018; 16: 1089-97, editorial 1037-39)) provide data from 151 children who underwent multiple modalities to assess their Crohn’s disease (CD) (ImageKids Study group).

Key findings:

  • MRE and ileocolonoscopy had concordance in 69% of cases.  55% had neither transmural nor mucosal healing, 14% had both transmural and mucosal healing.
  • MRE did not show features of active disease in 25% that was identified on ileocolonoscopy.  This is an expected finding given the ability of endoscopy (& capsule endoscopy) to identify milder mucosal lesions more precisely.
  • MRE did show evidence of disease in 6% who had unremarkable ileocolonoscopy (mucosal healing)
  • Calprotectin at a cut-off of 100 mcg/mL had 71% sensitivity and 92% specificity for diagnosing mucosal and transmural healing whereas a level of 300 mcg/mL had a sensitivity of 80% and specificity of 81%.

My take: This study confirms the complementary nature of cross-sectional imaging with endoscopy to determine healing.  In addition, in children with CD, calprotectin levels of more than 100 mcg/mL could indicate the need for further assessment (if this would affect management).

This is in agreement with another recent post: IBD Reviews: Antibiotics and Biomarkers:  “a calprotectin has a high level of excluding active inflammation/IBD. In populations with IBD, levels more than 250 mcg/g indicate a high likelihood of active inflammation whereas levels between 100-250 are indeterminate.”

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Sunshine Meadows, Banff Nat’l Parke

DGAT1 Deficiency

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Briefly noted: JM van Rijn et al. Gastroenterol 2018; 155: 130-43.  This study of 10 patients from 6 families (5 had consanguinity) was the largest cohort to date describing the clinical features in this disorder and used patient-derived fibroblasts and organoids to understand the pathophysiology.

Key clinical features:

  • Early-onset vomiting and/or diarrhea
  • Protein-losing enteropathy/hypoalbuminemia

Key finding in study:

  • These patients had altered lipid metabolism and were susceptible to lipid induced cell death.  Thus DGAT1 mutations cause congenital diarrhea and this is linked to fat intolerance.

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Sunshine Meadows, Banff Natl Park

Active Colitis More Likely in Children in Clinical Remission Who Have PSC and IBD

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A recent study (A Ricciuto et al. Clin Gastroenterol Hepatol 2018; 16: 1098-1105) provides more data regarding the lack of symptom correlation and inflammatory bowel disease (IBD) activity in children with primary sclerosing cholangitis (PSC).

In a prospective study of children with colonic IBD with and without PSC, the authors followed clinical features (eg. PUCAI), fecal calprotectin and endoscopy severity.

Key findings:

  • Patients with PSC-IBD (n=37) in clinical remission had higher endoscopic scores and greater odd of active endoscopic disease than IBD-only controls (n=50) (odds ratio 5.9, with CI 1.6-21.5)
  • Fecal calprotectin level <93 mcg/g were identified mucosal healing with 100% sensitivity and 92% specificity when compared with UC Endoscopic Index of Severity (UCEIS)

Overall, this study is in agreement with a prior adult study showing higher levels of active disease in those with PSC-IBD compared to those with IBD alone, despite clinical remission (Why does PSC increase the risk of colorectal cancer in UC?).

My take: Particularly in individuals with the combination of IBD-PSC, objective biomarkers (eg. Calprotectin) are needed to identify the accuracy of clinical remission; though, even in patients with IBD without PSC, objective biomarkers are needed as well due to the limitations of clinical symptom indices.

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Moraine Lake, Banff

Management of Pediatric Ulcerative Colitis -ESGHAN/ECCO Recommendations

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Two complementary articles provide extensive guidance on the management of ulcerative colitis and acute severe colitis:

  • D Turner et al. JPGN 2018; 67: 257-91
  • D Turner et al. JPGN 2018; 67: 292-310

Between the two articles there are more than 60 practice recommendations, more than 120 practice points, and more than 700 references.  As such, these articles are probably better for a journal review meeting rather than a brief blog post.

Figure 1 (2nd article, page 299) provides a handy algorithm for management of acute severe colitis:

  • On day 1-2, the algorithm recommends stool studies, starting methylprednisolone, and withholding 5-ASA.
  • On day 3, if PUCAI <45, suggests continuing steroid and transitioning to oral therapy when PUCAI <35.  On day 3, if PUCAI ≥45, the authors suggest screening for second line therapy, involve surgery (to discuss colectomy if there is nonresponse to medical treatment), and looking for CMV infection (eg. sigmoidoscopy).
  • On day 5, if PUCAI >65, recommendation is to start 2nd line Rx (eg. infliximab, tacrolimus, or cyclosporine). If PUCAI 35-65, continue corticosteroids for additional 2-5 days. The authors note that infliximab is preferred 2nd line Rx unless planning to transition to vedolizumab.
  • The authors recommend weaning corticosteroids when 2nd line Rx is started
  • The authors recommend addition of an immunomodulator for at least 6 months in responders to infliximab in effort to lower the risk of colectomy.
  • The authors state “urgent colectomy is recommended following failure of 1 second-line therapy.”

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.

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