Devendra Mehta

Pepsin, a Marker of Gastric Contents, Is Increased in Tracheal Aspirates From Preterm Infants Who Develop Bronchopulmonary Dysplasia

OBJECTIVE. The objective of this study was to study the association between pepsin in tracheal aspirate samples and the development of bronchopulmonary dysplasia in preterm infants. METHODS. Serial tracheal aspirate samples were collected during the first 28 days from mechanically ventilated preterm neonates. Bronchopulmonary dysplasia was defined as the need for supplemental oxygen at 36 weeks’ postmenstrual age. An enzymatic assay with a fluorescent substrate was used to detect pepsin. Total protein was measured by the Bradford assay to correct for the dilution during lavage. Immunohistochemistry using antibody against human pepsinogen was performed in 10 lung tissue samples from preterm infants. RESULTS. A total of 256 tracheal aspirate samples were collected from 59 preterm neonates. Pepsin was detected in 234 (91.4%) of 256 of the tracheal aspirate samples. Twelve infants had no bronchopulmonary dysplasia, 31 infants developed bronchopulmonary dysplasia, and 16 infants died before 36 weeks’ postmenstrual age. The mean pepsin concentration was significantly lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks’ postmenstrual age. Moreover, the mean pepsin level was significantly higher in infants with severe bronchopulmonary dysplasia compared with moderate bronchopulmonary dysplasia. The mean pepsin level in tracheal aspirate samples from the first 7 days was also lower in infants with no bronchopulmonary dysplasia compared with those who developed bronchopulmonary dysplasia or developed bronchopulmonary dysplasia/died before 36 weeks’ postmenstrual age. Pepsinogen was not localized in the lung tissues by immunohistochemistry. CONCLUSION. The concentration of pepsin was increased in the tracheal aspirate of preterm infants who developed bronchopulmonary dysplasia or died before 36 weeks’ postmenstrual age. Recovery of pepsin in tracheal aspirate samples is secondary to gastric aspiration, not by hematogenous spread or local synthesis in the lungs. Chronic aspiration of gastric contents may contribute in the pathogenesis of bronchopulmonary dysplasia.

Pepsin, a reliable marker of gastric aspiration, is frequently detected in tracheal aspirates from premature ventilated neonates: relationship with feeding and methylxanthine therapy.

Objectives: To determine the frequency of pepsin detection in tracheal aspirate (TA) samples of mechanically ventilated premature neonates and its association with feedings and methylxanthine therapy. Patients and Methods: Serial TA samples (days 1, 3, 5, 7, 14, 21, 28 and >28vdays) were collected from premature neonates receiving ventilatory support. An enzymatic assay with a fluorescent substrate was used to detect pepsin. Pepsin was also measured in 10 serum samples collected in conjunction with the TA samples from 8 neonates. Results: A total of 239 TA samples was collected from 45 premature neonates (mean birth weight, 762 ± 166 g; mean gestational age, 25.5 ± 1.5 wk). Pepsin was detectable in 222 of 239 TA samples (92.8%) and in none of the serum samples. Pepsin was significantly lower on day 1 (mean, 170 ± 216 ng/mL) when compared with all other time points (P < 0.05). Mean concentration of pepsin was significantly lower when infants were unfed (265 ± 209 ng/mL) compared with levels during feeding (390 ± 260 ng/mL, P = 0.02). The mean level of pepsin was significantly higher in infants during xanthine therapy (419 ± 370 ng/mL) compared with no xanthine therapy (295 ± 231 ng/mL, P = 0.037). Conclusion: Pepsin, a marker of gastric contents, was detected in more than 92% of TA samples from premature infants on mechanical ventilation. The level of pepsin was higher in fed infants when compared with unfed infants. Xanthine therapy was also associated with increased pepsin in TA samples. Chronic aspiration of gastric contents may worsen lung disease in premature infants.

Are There Psychosocial Differences in Diagnostic Subgroups of Children with Recurrent Abdominal Pain

Objectives: To examine psychosocial differences in diagnostic subgroups of children with recurrent abdominal pain (RAP). Methods: Children meeting Apleys 1975 definition of RAP were divided according to physician ratings into three subgroups, based on the Rome II diagnostic criteria of functional gastrointestinal disorders: functional dyspepsia (n = 17), irritable bowel syndrome (n = 18), and functional abdominal pain (n = 27). Groups were compared using measures of (a) child psychopathology, (b) parent psychopathology, and (c) child pain, somatization, and functional disability. Results: Multivariate results from a discriminant function analysis demonstrated that children classified according to these criteria could not be differentiated with respect to parent reported child psychopathology or child pain, somatization, and functional disability. There were significant univariate differences, however, between groups on parental psychopathology (F = 4.39, P = 0.02); parents of children with functional dyspepsia reported greater parental psychopathology symptoms than the other two groups. Conclusions: This study provides a preliminary comparison of pain, somatization, functional impact, and psychopathology ratings in the Rome II diagnostic subclassifications of children with RAP. Further investigation utilizing larger sample sizes, pain measures specifying pain location, and parental modeling of somatic behavior is indicated to better understand potential similarities and differences between these subgroups.

Primary Sclerosing Cholangitis and Multiple Autoimmune Disorders in a Patient With Down Syndrome

1 Department of Pediatric Gastroenterology, Hahnemann University Hospital, Phildelphia, Pennsylvania; 2 Department of Pediatric Gastroenterology, University of Maryland, Baltimore; 3 Department of Pediatrics, Hahnemann University Hospital; 4 Department of Pediatric Gastroenterology, University of Maryland; 5 Division of Pediatric Gastroenterology, Wyler Children’s Hospital, The University of Chicago, Illinois

An Automated Method for the Determination of Intestinal Disaccharidase and Glucoamylase Activities

Determination of disaccharidase and glucoamylase activities is important for the diagnosis of intestinal diseases. We adapted a widely accepted manual method to an automated system that uses the same reagents reaction volumes, incubation times, and biopsy size as the manual method. A dye was added to the homogenates as the internal quality control to monitor the pipetting precision of the automated system. When the automated system was tested using human intestinal homogenates, the activities of all the routinely tested disaccharidases, including lactase, maltase, sucrase, and palatinase, as well as the activity of glucoamylase, showed perfect agreement with the manual method and were highly reproducible. The automated analyzer can perform the same routine assays of disaccharidases and glucoamylase with high consistency and accuracy and reduce testing costs by performing a larger sample size with the same number of staff. Additional developments, such as barcoding and built-in plate reading, would result in a completely automated system.

1090: ASSOCIATION BETWEEN INTUBATION FACTORS AND ASPIRATION AND VENTILATOR-ASSOCIATED CONDITIONS

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: Tracheal intubation in the prehospital setting has been associated with increased risk for aspiration. Using data from an ongoing study, we evaluated tracheal intubation variables with tracheal amylase and pepsin A (aspiration), and ventilatorassociated conditions (VAC). We hypothesized that subjects intubated in the field would have higher rates of aspiration and VAC. Methods: Intubation and outcome data were collected as part of an ongoing oral suction trial in ventilated patients. Consent was obtained from patient or legal proxy. Adult subjects (≥ 18) were enrolled within 24 hours of oral intubation and followed while intubated, up to 14 days. Documented aspiration at time of intubation was an exclusion criterion. Primary outcomes were tracheal amylase and VAC (NHSN criteria). Tracheal pepsin A values were evaluated in a subset (n = 84). Data were analyzed with chi-square and ANOVA. Results: Data were analyzed from 368 subjects: mean age 57.7 (18.7) years, 56.3% male, 74.2% white, 19.3% Hispanic. Intubation location was study site (82.9%), other hospital (9.2%), and field (7.9%). The ICU (39.9%) and ED (37.8%) were the most common units. Most patients (76.4%) had a positive amylase (≥ 396 IU/L) while 16.7% had a positive pepsin A (≥ 6 ng/mL) in baseline tracheal specimens. Although not significant, mean tracheal amylase values were highest for field intubations (p = 0.64); mean tracheal pepsin A values were highest for intubations at the study site (p = .61) and if more than one intubation attempt was required (p = .11). VAC rates were significantly higher for other hospital intubations (29.4%) compared with study site (11.1%) or field (10.3%, p = 0.009), and for those that required more than one intubation attempt (21.3% vs 10.0%; p = .02). Conclusions: Aspiration of oral and gastric contents was observed despite exclusion criterion of no documented aspiration during intubation. Strategies to ensure successful intubation with one attempt are needed. Further research is warranted to identify clinical implications of aspiration and explore VAC rates associated with interhospital transfers. (1R01NR014508)

New developments in acute diarrhea

Introduction Diarrhea is defined as excess stool water, usually greater than 200 gm/day (or greater than 10 gmikglday in infants). Frequency per se, is not indicative of diarrhea, although they often coexist. Indeed, breast-fed infants may have up to 12 stools/day, and formula-fed infants, up to seven stools/day. The presence of undigested food particles merely indicates fast transit. Acute infective diarrhea is usually an obvious increase over the baseline with nausea, vomiting, fever, and abdominal pain variably present. Although most of the episodes in children are self-limited, diarrhea continues to be a major global problem, accounting for up to 3.5 million deaths in children less than 5 years old worldwide.’ In the United States, 220,000 patients are hospitalized per year, accounting for 10.6% of admissions in this age group, whereas most of the 300 to 400 deaths per year attributed to diarrhea occur in the first year.’ The established pathogens of pediatric diarrhea are listed in Table 1. In up to 40% of presumed acute infective diarrhea, no pathogen is isolated. Epidemiology is important in predicting likely pathogens, especially in terms of age, geography, season, water source, travel, and day-care exposure. The current approach to diarrhea in childhood is to establish whether we are dealing with a secretory or osmotic (malabsorptive) process. The immediate problem is to avoid or correct dehydration. High fever, particularly with bloody diarrhea, requires investigation for possible bacteremia and sepsis. Furthermore, documentation of the causative organism, bacterial, viral, or parasitic, is mandatory in infants. The susceptibility of young infants to bacterial toxins is becoming more apparent. On the one hand, the greater susceptibility of infants to enterotoxigenic Escherichia co/i is due to higher density of guanylate cyclase-associated receptors in the small intestinal enterocytes. On the other hand, Shiga toxin of shigellosis does not affect the infant as much because of underdeveloped glycolipid receptors on the enterocytes. Unusual organisms in the stool, like persistent cryptosporidium might raise the suspicion of AIDS and immunodeficiency. Nonspecific diarrhea may be a symptom of infection elsewhere, such as pneumonia, otitis media, and appendicitis, and is generally not dehydrating unless it coexists with anorexia and vomiting. Noninfectious causes such as dietary indiscretion, especially overfeeding and the use of large quantities of fruit juices that include fructose, sorbitol, and sucrose may precipitate diarrhea, and food poisoning from preformed toxins tend to cause brief problems (botulism an important exception) and may be suspected from the history. Ingestion of drugs and chemicals, for example, heavy metals, should always be considered. Many proprietary antipyrexial elixirs contain sig-