Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice.

We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development.

Chest physiotherapy, gastro-oesophageal reflux, and arousal in infants with cystic fibrosis.

BACKGROUND: Postural drainage chest physiotherapy in infants with cystic fibrosis (CF) exacerbates gastro-oesophageal reflux (GOR) and may contribute to a more rapid deterioration in lung function. AIMS: To compare standard postural drainage chest physiotherapy (SPT) and a modified physiotherapy regimen (MPT) without head-down tilt, with regard to GOR, arousal state, and cardiorespiratory function. METHODS: Twenty infants with CF underwent 30 hour oesophageal pH monitoring, during which four chest physiotherapy sessions were administered (day 1: MPT-SPT; day 2: SPT-MPT). Arousal state, heart rate, and oxygen saturation were documented for each of the physiotherapy positions (supine, prone, right lateral, and left lateral with (SPT) or without (MPT) 30 degrees head-down tilt). RESULTS: Significantly more reflux episodes occurred during SPT than during MPT, but there were no significant differences in median episode duration or fractional reflux time. During SPT, left lateral positioning was associated with fewer reflux episodes compared to other positions. During supine and prone positioning, more reflux episodes occurred during SPT than during MPT. Infants were significantly more likely to be awake or cry during SPT. There was a significant association between crying and reflux episodes for SPT. Non-nutritive sucking was associated with a significant reduction in reflux episodes during SPT. Oxygen saturation during SPT was significantly lower during crying and other waking, and non-nutritive sucking during SPT was associated with a significant increase in oxygen saturation. CONCLUSIONS: SPT is associated with GOR, distressed behaviour, and lower oxygen saturation.

Brachyspira aalborgi infection in four Australian children.

AIM: The clinical presentation of four children and adolescents (two males and two females with a mean age of 12.4 years; range 9-16 years) with colorectal spirochetosis is discussed. RESULTS: Symptoms included persistent diarrhea (n = 2), rectal bleeding (n = 1) and abdominal pain (n = 2). In all patients, colorectal spirochetosis was an unanticipated finding on colonic histology, and the presence of spirochetes was confirmed by the use of electron microscopy. Spirochetes were identified as Brachyspira aalborgi by using PCR amplification of the bacterial 16S rRNA and nicotinamide adenine dinucleotide oxidase sequences in all four patients. No other enteric pathogens were found. CONCLUSIONS: Although all patients appeared to respond to antibiotic treatment, the clinical significance of B. aalborgi as a human pathogen requires further investigation.

Postural drainage in cystic fibrosis: is there a link with gastro-oesophageal reflux?

OBJECTIVES: To determine the clinical effects of a change from postural drainage (PD) to positive expiratory pressure chest physiotherapy (PEP) in children with cystic fibrosis (CF) and symptoms of gastro-oesophageal reflux (GOR). To measure the effects of PD on GOR in children with CF. METHODS: Study 1: Six adolescents with CF and symptoms of GOR during PD were changed to upright PEP physiotherapy. The effects on lung function, reflux symptom scores and annual hospital days were measured. Study 2: Twenty-four children with CF (mean age 11 years) and symptoms suggestive of GOR underwent 24-h pH monitoring, including periods of chest physiotherapy. RESULTS: Study 1: All six patients reported a reduction in reflux symptoms during PEP therapy (P < 0.001). Lung function parameters improved during the first 6 months of PEP (P < 0.001). This improvement was sustained for a further 18 months. Annual hospital days decreased significantly (P < 0.0005). Study 2: Nine of 24 patients (37.5%) had pathological GOR. Reflux episodes were significantly increased during PD (P < 0.0001), as was fractional reflux time (P < 0.01). CONCLUSIONS: Upright PEP physiotherapy may be more appropriate than PD in selected patients with CF and symptomatic GOR. The role of GOR as a cofactor in the progression of pulmonary disease in CF needs further evaluation.

Multiresistant Pseudomonas aeruginosa outbreak in a pediatric oncology ward related to bath toys.

BACKGROUND: Nosocomial outbreaks of Pseudomonas aeruginosa in pediatric hospitals frequently involve neonates and immunosuppressed patients and can cause significant morbidity and mortality. OBJECTIVE: To describe the investigation of a multidrug-resistant P. aeruginosa outbreak in a pediatric oncology ward at the Royal Children's Hospital, Melbourne, Australia. DESIGN AND METHODS: Specimens were collected from infected patients and the ward environment. Bacterial isolates were characterized by antibiotic susceptibility patterns and bacterial DNA fingerprinting performed by pulsed-field gel electrophoresis (PFGE). A case-control study was carried out to assess possible risk factors for infection. RESULTS: Eight patients had clinical illnesses including bacteremia (n = 5) and infections of skin (n = 2), central venous catheter site (n = 1) and urinary tract (n = 1). The environmental ward survey yielded isolates of multiresistant P. aeruginosa from a toy box containing water-retaining bath toys, as well as from three of these toys. Pulsed-field gel electrophoresis of bacterial DNA demonstrated identical band patterns of the isolates from patients, toys and toy box water. A case-control study involving the 8 cases and 24 disease-matched controls demonstrated a significant association between P. aeruginosa infection and use of bath toys (P = 0.004), use of bubble bath (P = 0.014), duration of stay (P = 0.007) and previous antibiotic exposure (P = 0.026). Cultures from the bubble bath liquid were negative. CONCLUSION: This is the first description of a nosocomial outbreak associated with toys. We caution against the use of water-retaining bath toys in wards treating immunocompromised children.

Gastro-oesophageal reflux in infants under 6 months with cystic fibrosis.

AIM: To establish the incidence of pathological gastro-oesophageal reflux (GOR) in newly diagnosed infants with cystic fibrosis and to identify clinical predictors of increased reflux. METHODS: 26 infants with cystic fibrosis less than 6 months of age (14 male, 12 female; mean (SEM) age 2.1 (0.21) months, range 0.8 to 5.6 months) underwent prolonged oesophageal pH monitoring (mean duration 27.1 (0.49) hours; range 21.3 to 30.2 hours). Reflux symptoms, anthropometric variables, pancreatic status, meconium ileus, genotype, and chest x ray findings were correlated with pH monitoring data. RESULTS: Five infants (19.2%) had an abnormal fractional reflux time of greater than 10%, seven (26.9%) of 5-10%, and 14 (53.8%) of below 5%. Infants who presented with frequent vomiting had a significantly higher fractional reflux time than infants who had infrequent or no vomiting. There was no significant association between abnormal chest x rays and pathological GOR. Sex, genotype, nutritional status, meconium ileus, and pancreatic enzyme supplementation were not significantly associated with pathological GOR. CONCLUSIONS: About one in five newly diagnosed infants with cystic fibrosis had pathological GOR. Pathologically increased reflux was present before radiological lung disease was established. Apart from frequent vomiting, no useful clinical predictors of pathological reflux were found.

Postural drainage and gastro-oesophageal reflux in infants with cystic fibrosis.

UNLABELLED: Gastro-oesophageal reflux is increased in cystic fibrosis and it is possible that postural drainage techniques may exacerbate reflux, potentially resulting in aspiration and further impairment of pulmonary function. AIM: To evaluate the effects of physiotherapy with head down tilt (standard physiotherapy, SPT) on gastroesophageal reflux and to compare this with physiotherapy without head down tilt (modified physiotherapy, MPT). METHOD: Twenty (mean age 2.1 months) infants with cystic fibrosis underwent 30 hour oesophageal pH monitoring during which SPT and MPT were carried out for two sessions each on consecutive days. RESULTS: The number of reflux episodes per hour, but not their duration, was significantly increased during SPT compared with MPT (SPT 2.5 (0.4) v MPT 1.6 (0.3), p = 0.007) and to background (1.1 (0.)1, p = 0.0005). Fractional reflux time was also increased during SPT (11.7 (2.6)%) compared with background (6.9 (1.3)%) p = 0.03) but not compared with MPT (10.7 (2.7)%). There was no significant difference between MPT and background for number of reflux episodes, their duration, or fractional reflux time. CONCLUSIONS: SPT, but not MPT, was associated with a significant increase in gastro-oesophageal reflux in infants with cystic fibrosis.

Role of gastro-oesophageal reflux in infant irritability.

Gastro-oesophageal reflux (GOR) disease may cause excessive crying in infants. The role of GOR was evaluated in infant irritability and an attempt was made to define clinical predictors of pathological reflux. Seventy consecutively admitted infants with irritability and presumptive GOR were retrospectively reviewed. All had undergone prolonged oesophageal pH monitoring. Pathological GOR was defined as a fractional reflux time of > or = 10% and was significantly less common in infants under 3 months (one of 24; 4.2%) than in older infants (10 of 46; 21.7%). All infants with pathological GOR presented with frequent vomiting, and 'silent' pathological reflux did not occur. Poor weight gain, feeding refusal, backarching, and sleep disturbance were not significantly associated with pathological GOR. The results suggest that pathological GOR is an unlikely cause of infant irritability under the age of 3 months.