Major basic protein is a useful marker to distinguish eosinophilic esophagitis from IBD-associated eosinophilia in children.

OBJECTIVES: The incidence of eosinophilic esophagitis (EoE) is 3-5 times greater in patients with inflammatory bowel disease (IBD) compared with the general population. This study aimed to differentiate true EoE from esophageal eosinophilia in IBD patients by evaluating expression of major basic protein (MBP) and interleukin-13 (IL-13) in esophageal biopsies. METHODS: This retrospective study included subjects who had an esophagogastroduodenoscopy with esophageal biopsies for IBD work up or suspicion for EoE. Patients were classified into 5 groups: EoE with ≥15 eosinophils per high power field (eos/hpf), EoE-IBD with ≥15 eos/hpf, IBD eosinophilia with 1-14 eos/hpf, IBD and control groups. Biopsies were stained with MBP and IL-13 antibodies and the results (% staining/total tissue area), demographic, and clinical findings were compared among the groups. RESULTS: The median for MBP staining levels in EoE-IBD was 3.8 (interquartile range 1.3-23), significantly lower than in EoE at 52.8 (8.3-113.2), but higher than in IBD eosinophilia at 0.2 (0-0.9; p < 0.001) and negligible in the IBD and control groups. IL-13 expression in EoE was significantly higher only compared with IBD and controls not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity while IL-13 had 83% sensitivity and 90% specificity using cutoff point from the cohort without EoE-IBD patients. Based on MBP cutoff point that distinguished EoE from non EoE, 56% in EoE-IBD were MBP-positive whereas 100% in EoE group (p < 0.05). CONCLUSIONS: MBP may be an excellent marker in distinguishing true EoE from eosinophilia caused by IBD. Our data implied that MBP together with endoscopic and histologic changes can assist EoE diagnosis in IBD patients.

Oncostatin-M Does Not Predict Treatment Response in Inflammatory Bowel Disease in a Pediatric Cohort.

OBJECTIVES: This study aimed to determine whether mRNA expression of oncostatin-M (OSM) and its receptor (OSMR) in initial, pre-treatment intestinal biopsies is predictive of response to tumor necrosis factor antagonists (anti-TNF) in a pediatric inflammatory bowel disease (IBD) cohort. Secondary outcomes correlated OSM and OSMR expression with demographic variables; IBD type, extent, phenotype, and severity; laboratory values; and endoscopic findings. METHODS: A retrospective chart review was conducted on 98 pediatric patients. Patients' clinical courses were stratified as follows: failed anti-TNF (n = 14), quiescent on anti-TNF (n = 36), anti-TNF naïve (n = 19), and age-matched non-IBD controls (n = 29). The mRNA from each patient's pre-treatment ileal or colonic biopsy was isolated, and expression of OSM and OSMR was analyzed. RESULTS: There was no difference in OSM or OSMR expression among the three IBD groups; however, expression was significantly higher in patients with IBD than non-IBD controls (P < 0.001). OSM and OSMR were more highly expressed in patients with ulcerative colitis (UC) with a Mayo score of 3 (P = 0.0092 and P = 0.0313, respectively). High OSM expression correlated with severe disease activity indices at diagnosis (P = 0.002), anemia at diagnosis (P = 0.0236), and need for immunomodulators (P = 0.0193) and steroids (P = 0.0273) during patients' clinical courses. CONCLUSIONS: OSM and OSMR expression were not predictive of response to anti-TNF in our pediatric cohort. OSM expression did correlate with IBD compared with healthy controls as well as with several clinical indicators of severe IBD.

Salivary pepsin A detection related to gastro-oesophageal reflux episodes in children undergoing impedance probe monitoring.

AIM: Gastro-oesophageal reflux is routinely diagnosed with invasive intraluminal impedance pH probe monitoring. This study aimed to determine whether gastric pepsin A detected in saliva of children correlates with gastro-oesophageal reflux. METHODS: Patients undergoing probe monitoring were prospectively recruited between 2014 and 2016 at a paediatric hospital. Standard impedance and demographic data were obtained from electronic medical records. Salivary samples were collected during impedance and measured for gastric pepsin A with an enzyme-linked immunosorbent assay. Impedance probe and pepsin data were analysed and compared for correlation. RESULTS: From 52 enrolled subjects, 28 males and 24 females with mean age 8.0 ± 5.9 and range 0.58-18.0 years, 417 salivary samples were collected. Positive pepsin was found in 14% of samples and 48% patients. The sensitivity of pepsin A in predicting an abnormal impedance was 43% and specificity, 50%. Among pepsin A positive samples, 72% corresponded with a gastro-oesophageal reflux episode. Pepsin peak levels significantly correlated with acidic reflux. CONCLUSION: Pepsin A was presented in saliva of children undergoing gastro-oesophageal reflux disease investigation. Positive pepsin A was associated with a gastro-oesophageal reflux episode, and its peak value correlated with acidic reflux. Salivary pepsin as a marker for gastro-oesophageal reflux needs further investigation.

Long non-coding RNA00882 contributes to platelet-derived growth factor-induced proliferation of human fetal airway smooth muscle cells by enhancing Wnt/ß-catenin signaling via sponging miR-3619-5p.

Long non-coding RNAs (lncRNAs) are emerging as novel and critical regulators in the pathogenesis of asthma. However, the precise role of lncRNAs in pediatric asthma remains largely unknown. In this study, we aimed to investigate the biological function of lncRNA00882 (LINC00882) in regulating the proliferation of fetal airway smooth muscle (ASM) cells, which play an important role in airway remodeling during asthma development. Herein, we found that LINC00882 expression was significantly up-regulated in ASM cells stimulated with platelet-derived growth factor (PDGF). Functional experiments showed that the knockdown of LINC00882 markedly reduced the proliferation of fetal ASM cells induced by PDGF, while the overexpression of LINC00882 exhibited the opposite effect. Bioinformatics analysis, the luciferase reporter assay and the RNA pull-down assay revealed that LINC00882 directly interacted with microRNA-3619-5p (miR-3619-5p). LINC00882 negatively regulated miR-3619-5p expression in fetal ASM cells. Notably, ß-catenin was identified as a target gene of miR-3619-5p. miR-3619-5p overexpression restricted PDGF-induced cell proliferation through inhibiting Wnt/ß-catenin signaling. Moreover, miR-3619-5p overexpression significantly attenuated the LINC00882-induced promotion effect on PDGF-induced cell proliferation and Wnt/ß-catenin signaling in fetal ASM cells. In contrast, miR-3619-5p inhibition significantly reversed the LINC00882 knockdown-mediated inhibitory effect on PDGF-induced cell proliferation and Wnt/ß-catenin signaling. Taken together, our results demonstrate that LINC00882 promotes PDGF-induced cell proliferation of ASM cells by enhancing Wnt/ß-catenin signaling via sponging miR-3619-5p, suggesting a potential role for LINC00882 in airway remodeling in pediatric asthma.

Heat shock protein 70 is induced by pepsin via MAPK signaling in human nasal epithelial cells.

BACKGROUND: Recent studies have shown that laryngopharyngeal reflux is associated with chronic rhinosinusitis. Pepsin may be a key factor involved in the injury of nasal mucosal epithelial cells, but the pathogenesis remains unclear. We are to investigate whether a mitogen-activated protein kinase (MAPK) pathway regulates heat shock protein 70 (HSP70) expression in primary cultures of human nasal epithelial cells (HNEpCs) in response to pepsin stimulation. METHODS: HSP70 protein expression levels in HNEpCs were estimated by Western blot analysis after treatment with pepsin. MAPK pathway activity levels were also evaluated to elucidate the mechanism underlying the effects of pepsin on HSP70 in HNEpCs. Inhibitors of signaling pathways were used to determine the contribution of MAPKs in HSP70 response after pepsin stimulation. Cellular apoptosis and cell viability in HNEpCs after treatment with pepsin were measured. RESULTS: The expression of HSP70 increased after stimulation with pepsin and decreased after the removal of pepsin. Pepsin induced activation of p38, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase (JNK) 1/2. Inhibition of JNK1/2 reduced HSP70 expression in HNEpCs. The apoptosis in HNEpCs at 12 h after treatment with pepsin at pH 7.0 increased significantly when compared with the control and pH 7.0 groups. Cell viability decreased following exposure to pepsin at pH 7.0. CONCLUSION: Pepsin, even under neutral pH 7.0, increases the expression of HSP70 in HNEpCs by activating the JNK/MAPK signaling pathway. Increased HSP70 may be the protective mechanism when pepsin presents in the other parts of the body.

Pilot Study Measuring the Novel Satiety Hormone, Pro-Uroguanylin, in Adolescents With and Without Obesity.

OBJECTIVE: Disruption of satiety signaling may lead to increased caloric intake and obesity. Uroguanylin, the intestinal hormone, travels as a precursor to the central nervous system where it activates guanylyl cyclase C and stimulates pro-satiety neurons. Rodent studies have demonstrated that guanylyl cyclase C-knockout mice overeat and have increased weight gain versus wild-type mice and hyper-caloric obesity diminishes uroguanylin expression. We measured circulating plasma pro-uroguanylin, along with other gastrointestinal peptides and inflammatory markers, in human adolescents with and without obesity, as a pilot study. We hypothesized that adolescents with obesity would have less circulating pro-uroguanylin than adolescents without obesity have. METHODS: We recruited 24 adolescents (age 14-17 years) with and without obesity (body mass index >95% or body mass index <95%) and measured plasma pro-uroguanylin at fasting and successive time points after a meal. We measured 3 other satiety hormones and 2 inflammatory markers to characterize overall satiety signaling and highlight any link between uroguanylin and inflammation. RESULTS: Female adolescents with obesity had lower circulating pro-uroguanylin levels than female adolescents without obesity; we observed no difference in males. Other measured gastrointestinal peptides varied in their differences between cohorts. Inflammatory markers were higher in female participants with obesity. CONCLUSIONS: In adolescents with and without obesity, we can measure circulating pro-uroguanylin levels. In female adolescents without obesity, levels are particularly higher. Pro-uroguanylin secretion patterns differ from other circulating gastrointestinal peptides. In female adolescents with obesity, inflammation correlates with decreased pro-uroguanylin levels.

Effect of 90° counterclockwise rotation of the endotracheal tube on its advancement through the larynx during nasal fiberoptic intubation in children: a randomized and blinded study.

BACKGROUND: Resistance to the passage of the endotracheal tube (ETT) is frequently encountered in children as it is advanced over the fiberoptic scope for placement into the trachea because it gets hung up at the laryngeal inlet. Literature in adults indicates that a 90° counterclockwise rotation (CCR) of the ETT before advancing results in smooth passage. We found no literature in children. OBJECTIVES: Our aim was to study if a 90° counterclockwise rotation (CCR) of the ETT before advancement leads to smooth passage of the ETT into the larynx in children. METHODS: Following IRB approval, we performed this study in two parts: Part 1: An unblinded, observational, pilot study on 20 children scheduled for oral rehabilitation where we concurrently used a fiberoptic scope nasally and GlideScope orally. We visualized the ETT path and observed that 90° CCR allowed smooth passage without hang up. Part 2: A blinded and randomized study on 40 children to confirm if 90° CCR from the outset would improve passage of the ETT during nasal intubation with a fiberoptic scope in children. All children were divided into two groups: group S, ETT bevel facing left; group R, ETT bevel facing down. RESULTS: In Part 1, we observed that the ETT got hung up in 57% of children with standard bevel direction (facing left) and in 0% of children when prerotated. In Part 2, efficacy of prerotation was confirmed; the ETT got hung up in 50% of children in group S but in only 10.5% of children in group R. CONCLUSION: A change in ETT tip orientation from bevel facing left to facing down by 90° CCR, leads to a significantly higher first-attempt success rate by nasal approach in children. We believe the ETT should be rotated before insertion into the nostril to ensure that full 90° CCR of the tip has been accomplished.

Ghrelin and obestatin levels in children with failure to thrive and obesity.

OBJECTIVES: Ghrelin and obestatin are 2 gastric hormones with opposite effects on food intake and body weight. We investigated plasma ghrelin and obestatin in children with failure to thrive (FTT) and obesity as compared with age-matched controls. METHODS: A total of 63 children were included in the study: 13 with FTT, 17 with obesity, and 33 age-matched controls. Children fasted for at least 8 hours before specimen collection. Both hormones were measured using commercially available enzyme immunoassay kits. RESULTS: Ghrelin and obestatin levels in children with FTT were not significantly different from that of the age-matched controls (P >0.05). In children with obesity, the total ghrelin levels were significantly lower (P = 0.0003) and the obestatin levels significantly higher (P = 0.029) compared with those in controls. In the control group, the fasting ghrelin level was significantly higher in the younger (<3 years) than in the older children (>3 years; P = 0.0004). Obestatin levels correlated positively with weight-for-age percentiles in the obese group (P = 0.011) and negatively in the control group >3 years (P = 0.019). CONCLUSIONS: Compared with the levels in age-matched controls, fasting ghrelin and obestatin levels did not differ significantly in children with FTT. In the children with obesity, the decreased ghrelin and increased obestatin levels suggest a possible adaptive process to positive energy balance. Ghrelin had pronounced age-related changes, and obestatin was associated with the weight status. This may suggest that these 2 hormones use different mechanisms to regulate energy balance and weight.

Cough in asthma triggered by reflux episodes.

With combined pH and impedance monitoring, non-acid, as well as acid reflux episodes, are more commonly detected immediately prior to cough in asthma in children. Gastroesophageal reflux should be evaluated as a trigger for cough in difficult childhood asthma.

The Controversy of Pepsinogen A/Pepsin A in Detecting Extra-Gastroesophageal Reflux.

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

Comparison of fecal elastase-1 and pancreatic function testing in children.

OBJECTIVES: The fecal pancreatic elastase-1 (FE-1) test is considered a simple, noninvasive, indirect measure of pancreatic function. We aimed to evaluate the performance of the FE-1 test compared with the direct pancreatic function test (PFT) with secretin stimulation in children. METHODS: Data of 70 children (6 months-17 years of age) who had both FE-1 test and PFT were analyzed. RESULTS: The average FE-1 concentration was 403 ±â€Š142 µg/g. Eleven children had concentrations below 200  µg/g, 23 between 201 to 500 µg/g, and 36 were above 500 µg/g. The average pancreatic elastase activity measured on direct stimulation was 49.1 ±â€Š38.6  µmol ·â€Šmin (-1)·â€Šml(-1) and 11 children had activity below the established cutoff (10.5 µmol ·â€Šmin(-1) ·â€Šml(-1)). Among the 11 children with pathologic PFT, 7 had normal FE-1, 4 were in the intermediate range (201-500 µg/g), and none were in the low range (<200 µg/g). Among the 59 children with normal direct PFT 11 (19%) had pathologic (<200 µg/g) and 19 (32%) had intermediate FE-1 tests. Twenty-nine children had both normal FE-1 concentration and normal PFT, giving a negative predictive value of 80%. The correlation between pancreatic elastase activity and FE-1 concentration was poor (r = 0.190). The sensitivity of the FE-1 test was found to be 41.7%, whereas the specificity was 49.2%. The positive predictive value of the FE-1 test was only 14%. CONCLUSIONS: The FE-1 test is a simple, noninvasive, indirect method; however, ordering physicians should be aware of its limitations. It can give false-positive results and has low sensitivity in children with mild pancreatic insufficiency without cystic fibrosis and in those with isolated pancreatic enzyme deficiencies.

Predictors of postoperative systemic inflammatory response syndrome after scoliosis surgery in adolescents with cerebral palsy: A retrospective analysis.

Background: Systemic inflammatory response syndrome (SIRS) is known to complicate postsurgical intensive care patients. We noticed that roughly half children with cerebral palsy who undergo posterior spinal fusion (PSF) for neuromuscular scoliosis developed SIRS in the intensive care unit. There is a paucity of literature detailing the impact of intraoperative causes of postoperative SIRS and downstream consequences in these patients. Study purpose was to understand the factors associated with SIRS in children who undergo PSF for neuromuscular scoliosis. Methods: This retrospective, case control study included children who underwent PSF for neuromuscular scoliosis. Patients with idiopathic scoliosis, osteogenesis imperfecta, and tracheotomy were excluded. Subjects were divided into two study groups based on the diagnosis of SIRS in the intensive care unit. Descriptive statistical analysis was used to identify factors associated with SIRS; a regression analysis was used to further evaluate the independent and significant influence of these factors. Results: There was no significant difference in the demographic and other preoperative variables. However, total blood products (ml/kg) administered was significantly higher among the SIRS group compared with the non-SIRS group (54.4±41.0 vs 34.1±21.5 P <0.034). Percent of patients remaining intubated was greater in the SIRS group compared with the non-SIRS group (44.1% vs 7.0%, P < 0.001). The regression model revealed that the odds to develop SIRS in patients who were not extubated were 7.467-fold higher (CI: 1.534-36.347) compared with those who were extubated (p=0.013). Conclusions: The incidence of SIRS is significantly higher among the patients who were not extubated at the end of PSF surgery. Further prospective studies are needed to look at the factors that impede the ability to extubate these patients at the end of surgery.

Influence of Age and Type 1 Diabetes Mellitus on Serological Test for Celiac Disease in Children.

PURPOSE: Serological tests of tissue transglutaminase (TTG) and deamidated gliadin (DGP) antibodies for celiac disease diagnosis show conflicting correlation with histology in young children and in type 1 diabetes mellitus (T1DM). Tests' ability to predict histology and cutoff values based on age and T1DM was evaluated. METHODS: A retrospective study of children who had celiac serological tests between 6/1/2002 and 12/31/2014 at a pediatric hospital. RESULTS: TTG IgA displayed similar results in predicting histology between <4.0 and ≥4.0 years age groups with sensitivity 98% and 93%, and specificity 88% and 86%, respectively. In children <4.0 years old, sensitivity for DGP antibodies was 100% and specificity 94%; in ≥4.0 years age groups, sensitivity was 60%, 88% for DGP IgA and IgG and specificity 95%, 96%, respectively. TTG IgA had low specificity in patients with T1DM compared with non-T1DM, 42% vs. 91%. Positive TTG IgA with normal histology was associated with higher T1DM prevalence at 36% compared with negative tests at 4%. Finally, the TTG IgA cutoff value was higher in T1DM at 36 vs. 16.3 units in non-T1DM. DGP IgG cutoff showed similar values between age groups; TTG IgA and DGP IgA cutoffs were lower in <4.0 years at 8.3 and 11.9 units than ≥4.0 years at 23.4 and 19.9, respectively. CONCLUSION: TTG IgA is sufficient for the <4.0 years age group and DGP antibodies had no advantage over TTG IgA in older children. The cutoff value to determine a positive TTG IgA should be higher for children with T1DM.

The PNPLA3 rs738409 Variant but not MBOAT7 rs641738 is a Risk Factor for Nonalcoholic Fatty Liver Disease in Obese U.S. Children of Hispanic Ethnicity.

PURPOSE: The rs641738 C>T in membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) is implicated, along with the rs738409 C>G polymorphism in patatin-like phospholipase domain-containing protein 3 (PNPLA3), in nonalcoholic fatty liver disease (NAFLD). The association of these polymorphisms and NAFLD are investigated in Hispanic children with obesity. METHODS: Obese children with and without NAFLD were enrolled at a pediatric tertiary care health system and genotyped for MBOAT7 rs641738 C>T and PNPLA3 rs738409 C>G. NAFLD was characterized by the ultrasonographic presence of hepatic steatosis along with persistently elevated liver enzymes. Genetic variants and demographic and biochemical data were analyzed for the effects on NAFLD. RESULTS: Among 126 enrolled subjects, 84 in the case group had NAFLD and 42 in the control group did not. The two groups had similar demographic distribution. NAFLD was associated with abnormal liver enzymes and elevated triglycerides and cholesterol (p<0.05). Children with NAFLD had higher percentage of PNPLA3 GG genotype at 70.2% versus 31.0% in non-NAFLD, and lower MBOAT7 TT genotype at 4.8% versus 16.7% in non-NAFLD (p<0.05). PNPLA3 rs738409 C>G had an additive effect in NAFLD; however, MBOAT7 rs641738 C>T had no effects alone or synergistically with PNPLA3 polymorphism. NAFLD risk increased 3.7-fold in subjects carrying PNPLA3 GG genotype and decreased in MBOAT7 TT genotype. CONCLUSION: In Hispanic children with obesity, PNPLA3 rs738409 C>G polymorphism increased the risk for NAFLD. The role of MBOAT7 rs641738 variant in NAFLD is less evident.

Fresh frozen plasma-to-red blood cell ratio is an independent predictor of blood loss in patients with neuromuscular scoliosis undergoing posterior spinal fusion.

PURPOSE: In major trauma with massive blood loss, higher fresh frozen plasma (FFP)-to-red blood cell (RBC) ratios have been associated with improved morbidity and mortality. Our population of patients with neuromuscular scoliosis undergoing posterior spinal fusion (PSF) often lose volumes of blood considered massive, that is, half a blood volume in 3 hours. In this retrospective cohort study, we examined the association of FFP ratio with blood loss in this elective surgical population. METHODS: Patients with neuromuscular scoliosis undergoing PSF with unit rod fixation were identified from our anesthesia cases database. The patients were divided into two groups: the low FFP group received FFP-to-RBC≤0.5, and the high FFP group received FFP-to-RBC>0.5. After controlling for a false discovery rate in the univariate analysis, a logistic and linear regression was performed to understand the contribution of the significant factors associated with increased blood loss. RESULTS: Risk estimation showed that patients in the low FFP group were more likely to lose >120% blood volume (odds ratio, 3.87; 95% confidence interval, 2.03-7.38). Linear regression revealed that each unit of increase in FFP-to-RBC ratio was associated with a 27.5% (95% confidence interval, -43.12-11.89) mean reduction in blood volume loss. CONCLUSIONS: In our retrospective study, we found that FFP-to-RBC ratio was significant independent predictor of blood loss in this group of complex spine patients undergoing PSF. Thus, in patients with neuromuscular scoliosis undergoing posterior spine fusion, use of higher ratio of FFP to RBC may decrease blood loss.

Reflux-Aspiration in Chronic Lung Disease.

Microaspiration, or silent aspiration, is commonly suspected in patients with refractory respiratory symptoms, including unexplained chronic cough, asthma, chronic obstructive pulmonary disease, bronchiolitis, bronchiectasis, and idiopathic pulmonary fibrosis. This suspicion is driven by the high prevalence of gastroesophageal reflux in these otherwise disparate disorders. Frequently, patients receive aggressive treatment for gastroesophageal reflux disease as a means of treating their underlying respiratory conditions, even in the absence of overt symptoms of reflux. However, clinical trials have not demonstrated a clear impact on outcomes with this strategy, and in some instances there may be potential for harm. Mechanistic studies have increasingly used gastric biomarkers obtained directly from the airways to confirm the association between reflux and respiratory disease, but results are limited by methodologic flaws and correlation. The best evidence of aspiration directly causing respiratory disorders is the histopathologic detection of foreign bodies. For most of the other chronic respiratory disorders, microaspiration may be uncommon or a secondary aggravating factor, as in patients with acute exacerbations of chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis. In some cases, microaspiration is probably not a significant factor at all, such as in unexplained chronic cough. It is important to distinguish between conditions in which aspiration is primarily or directly causal and conditions in which aspiration may be indirectly aggravating, to help identify whether interventions targeting reflux and aspiration precautions should be recommended to patients. Our clinical review examines some of the evidence supporting reflux-aspiration as a mechanism for several chronic respiratory disorders and offers some management considerations when reflux-aspiration is suspected.

Report on the Short Endoscopic Exocrine Pancreatic Function Test in Children and Young Adults.

OBJECTIVES: Endoscopic pancreatic function test (ePFT) has been in use for exocrine function testing since the 1990s. In patients, short ePFT assesses acinar function, unlike the longer version for ductal function in adults. The present study summarizes characteristics of 1913 short ePFTs (S-ePFT) performed at 2 centers since 2001. METHODS: The main indications in patients presenting at ages infancy to 24.3 years, for the S-ePFT were failure to thrive, weight loss, diarrhea, and abdominal pain with bloating. Secretin was administered as bolus, and 4 aliquots of fluid were collected between 4 and 10 minutes after administration. Amylase, lipase, trypsin, and chymotrypsin activities were measured in the laboratory. RESULTS: The pH of consecutive samples increased by 0.3 to 0.7. Overall, 36.7% had abnormal S-ePFT with selective amylase deficiency (9.5%) and generalized enzyme deficiency (8.9%) being the most frequent. Retest reproducibility, repeatability, and clinical validity were high. By adding S-ePFT to endoscopy for the suspicion of malabsorption, the abnormal findings increased by 36.9%. CONCLUSIONS: Short ePFT assesses pancreatic acinar function in a reliable and clinically meaningful way in patients. Diagnostic yield of endoscopy increased substantially albeit with increased sedation time. By S-ePFT ductal function, cytokines and proteomics can also be assessed.

Gastric pepsin in middle ear fluid of children with otitis media: clinical implications.

Gastroesophageal reflux and extraesophageal reflux have been postulated to be involved in the pathogenesis of otitis media. This is supported by recent studies revealing the presence of gastric pepsin in the middle ear space of children with otitis media but not in control patients without otitis media. Reflux's role in otitis media appears to be most pronounced in younger children and those with purulent effusions.

A pilot randomized clinical trial assessing the effect of cricoid pressure on risk of aspiration.

INTRODUCTION: Patients at risk for microaspiration during elective intubation often receive cricoid pressure in the hopes of mitigating such risk. However, there is scarce evidence to either support or reject this practice. The objective of this investigation was to assess the effect of cricoid pressure on microaspiration and to inform the potential feasibility of conducting a larger, more definitive clinical trial. METHODS: This was a pilot randomized clinical trial set in the operating rooms of a tertiary referral hospital between August and October of 2014. Patients with risk factors for microaspiration (obesity, gastroesophageal reflux disease, or diabetes) were enrolled. The patients were randomized to either cricoid pressure or no cricoid pressure during induction of anesthesia with endotracheal intubation. Immediately after intubation, a sample of lower airway secretions was collected and analyzed for pepsin A. MAIN RESULTS: A total of 95 patients were evaluated, randomized and completed the study protocol. 46 were randomized to cricoid pressure and 49 to no cricoid pressure. Seven patients crossed-over treatment arms. A total of 18 (19.6%) patients met the pre-defined criteria for microaspiration. In both the intention-to-treat and per-protocol analyses, there were no statistically significant differences in the rate of microaspiration [OR (95% CI)] = 1.39 (0.49-3.92) and 1.30 (0.44-3.86), respectively. CONCLUSIONS: Utilizing pepsin A as a biomarker of aspiration, this pilot clinical trial did not find evidence for a reduced rate of aspiration or adverse clinical events with the administration of cricoid pressure during elective endotracheal intubation of patients with risk factors for microaspiration.