Roxanne Strachan

Bacterial causes of empyema in children, Australia, 2007-2009

Most infections were caused by non–7-valent pneumococcal conjugate vaccine serotypes.

Intestinal Inflammation and Impact on Growth in Children With Cystic Fibrosis

Objective: The aim of the study was to evaluate and compare faecal markers of intestinal inflammation in children with cystic fibrosis (CF), and determine whether intestinal inflammation adversely affects the nutritional phenotype. Methods: Faecal samples for markers of intestinal inflammation, calprotectin, S100A12, and osteoprotegerin, were collected from children with CF, healthy controls (HCs), and Crohn disease (CD). Associations between inflammatory markers and clinical and nutritional indices were determined in subjects with CF. Results: Twenty-eight children with CF (mean [standard deviation (SD)] 8.4 [3.3] years old, 22 pancreatic insufficient [PI]), 47 HC, and 30 CD were recruited. Mean (SD) faecal calprotectin in CF (94.3 [100.6] mg/kg) was greater than HC (26.7 [15.4] mg/kg, P < 0.0001), but lower than CD (2133 [2781] mg/kg, P = 0.0003). Abnormal faecal calprotectin was found in subjects only with PI (17/22 (77%), P = 0.001). There was no difference in faecal mean (SD) S100A12 (0.8 [0.9] vs 1.5 [2.2] mg/kg, P = 0.14) and osteoprotegerin concentrations (72.7 [52.2] vs 62.5 [0.0] pg/mL, P = 0.2) between CF and HC. Patients with CD had significantly elevated S100A12 and osteoprotegerin compared with CF and HC. Faecal calprotectin inversely correlated with both weight (r = −0.5, P = 0.003) and height z scores (r = −0.6, P = 0.002) in CF. Conclusions: The pattern of intestinal inflammation in CF is unique and distinct from inflammatory bowel disease, with elevated faecal calprotectin but normal faecal S100A12 and osteoprotegerin concentrations. The severity of intestinal inflammation, based on faecal calprotectin, significantly correlates with poor growth.

Assessment of the burden of paediatric empyema in Australia

Aims:  To investigate the change in incidence of childhood empyema and pneumonia in Australia, and ascertain the management trends in all hospitals caring for children with empyema.

Pleural fluid nucleic acid testing enhances pneumococcal surveillance in children

Background and objective:  National surveillance of invasive pneumococcal disease (IPD) includes serotyping Streptococcus pneumoniae (SP) isolates from sterile site cultures. PCR is more sensitive and can identify more SP serotypes (STs) in culture‐negative samples. The aim of this study was to determine whether enhanced surveillance of childhood empyema, using PCR, provides additional serotype information compared with conventional surveillance.

Expression of PPARγ and Paraoxonase 2 Correlated with Pseudomonas aeruginosa Infection in Cystic Fibrosis

The Pseudomonas aeruginosa quorum sensing signal molecule N-3-oxododecanoyl-l-homoserine lactone (3OC12HSL) can inhibit function of the mammalian anti-inflammatory transcription factor peroxisome proliferator activated receptor (PPAR)γ, and can be degraded by human paraoxonase (PON)2. Because 3OC12HSL is detected in lungs of cystic fibrosis (CF) patients infected with P. aeruginosa, we investigated the relationship between P. aeruginosa infection and gene expression of PPARγ and PON2 in bronchoalveolar lavage fluid (BALF) of children with CF. Total RNA was extracted from cell pellets of BALF from 43 children aged 6 months–5 years and analyzed by reverse transcription–quantitative real time PCR for gene expression of PPARγ, PON2, and P. aeruginosa lasI, the 3OC12HSL synthase. Patients with culture-confirmed P. aeruginosa infection had significantly lower gene expression of PPARγ and PON2 than patients without P. aeruginosa infection. All samples that were culture-positive for P. aeruginosa were also positive for lasI expression. There was no significant difference in PPARγ or PON2 expression between patients without culture-detectable infection and those with non-Pseudomonal bacterial infection, so reduced expression was specifically associated with P. aeruginosa infection. Expression of both PPARγ and PON2 was inversely correlated with neutrophil counts in BALF, but showed no correlation with other variables evaluated. Thus, lower PPARγ and PON2 gene expression in the BALF of children with CF is associated specifically with P. aeruginosa infection and neutrophilia. We cannot differentiate whether this is a cause or the effect of P. aeruginosa infection, but propose that the level of expression of these genes may be a marker for susceptibility to early acquisition of P. aeruginosa in children with CF.

A bedside assay to detect streptococcus pneumoniae in children with empyema

Empyema is a complication of pneumonia, commonly caused by Streptococcus pneumoniae.

Age-dependent variation of fecal calprotectin in cystic fibrosis and healthy children

BACKGROUND Fecal calprotectin may be used as a non-invasive method to assess the effect of novel therapies on the gut in cystic fibrosis (CF). METHOD Stools from CF patients and healthy controls (HC) (0-10years old) were prospectively collected for evaluation of temporal trends. RESULTS 130 CF samples (64 subjects) and 114 HC samples (101 subjects) were collected. Overall, fecal calprotectin levels were different in CF patients and HC from 0 to 10years (P=0.0002). Fecal calprotectin in CF was significantly lower than HC from 0 to 1years (P=0.03) and demonstrated an upward trajectory until 4years. From >4 to 10years calprotectin was consistently higher in CF patients compared with HC (P=0.007). CONCLUSIONS Fecal calprotectin levels in children with CF and HC were age-dependent and had distinct trajectories. Careful interpretation of calprotectin is required if used in drug trials for CF, particularly in children less than 4years old.

Age-related levels of fecal M2-pyruvate kinase in children with cystic fibrosis and healthy children 0 to 10 years old

BACKGROUND The pathogenesis of gut inflammation, bacterial dysbiosis and increased rates of malignancy in CF is unclear. Fecal M2-pyruvate kinase (M2-PK) is a biomarker indicative of cellular proliferation that may be raised in intestinal malignancy and inflammation. Biomarkers, including M2-PK, may be useful in assessing effects of novel therapies on the gastrointestinal tract. METHODS M2-PK was measured in stools collected from patients with CF and HC (0-10years). Linear mixed model analysis was used. RESULTS M2-PK levels did not significantly change in children with CF (36 patients, 77 samples) (P=0.998) or HC (45 patients, 45 samples) (P=0.21), over the age range 0-10years. Patients with CF had elevated M2-PK compared to HC (median [IQR; range]: 10.7 [5.7-28.6; 1.0-239.1] (n=77) vs. 1.0 [1.0-1.0; 1.0-50.0] (n=45) U/mL, respectively; P=0.001). CONCLUSIONS Fecal M2-PK was elevated in children with CF compared with HC during infancy and throughout childhood suggesting abnormalities in the CF gut exist in early life.

Absence of back to school peaks in human rhinovirus detections and respiratory symptoms in a cohort of children with asthma

Much of what is known about the seasonality of human rhinovirus (hRV) infections has been learned from the study of acute asthma exacerbations presenting to emergency care, including those among children at the start of the school term. Much less is known about the patterns of hRVs in the community. In this study, viruses and day‐to‐day symptoms of asthma and colds were monitored twice weekly in 67 children with asthma aged 5–12 years, over a 15 month period in Sydney, Australia. Overall hRV was detected in 314/1232 (25.5%) of nasal wash samples and 142/1231 (11.5%) of exhaled breath samples; of these, 231 and 24 respectively were genotyped. HRVs were detected with similar prevalence rate throughout the year, including no peak in hRV prevalence following return to school. No peaks were seen in asthma and cold symptoms using twice‐weekly diary records. However, over the same period in the community, there were peaks in asthma emergency visits both at a large local hospital and in state‐wide hospitalizations, following both return to school (February) and in late autumn (May) in children of the same age. This study suggests that hRV infections are common throughout the year among children, and differences in virus prevalence alone may not account for peaks in asthma symptoms. J. Med. Virol. 88:578–587, 2016.