Paediatrics (RCH) - Research Publications

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    Fecal microbial transplantation in a pediatric case of recurrent Clostridium difficile infection and specific antibody deficiency
    Loke, P ; Heine, RG ; McWilliam, V ; Cameron, DJS ; Tang, MLK ; Allen, KJ (WILEY-BLACKWELL, 2016-12)
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    Clinical Use of Probiotics in Pediatric Allergy (CUPPA): A World Allergy Organization Position Paper.
    Fiocchi, A ; Burks, W ; Bahna, SL ; Bielory, L ; Boyle, RJ ; Cocco, R ; Dreborg, S ; Goodman, R ; Kuitunen, M ; Haahtela, T ; Heine, RG ; Lack, G ; Osborn, DA ; Sampson, H ; Tannock, GW ; Lee, BW ; WAO Special Committee on Food Allergy and Nutrition, (Elsevier BV, 2012-11)
    BACKGROUND: : Probiotic administration has been proposed for the prevention and treatment of specific allergic manifestations such as eczema, rhinitis, gastrointestinal allergy, food allergy, and asthma. However, published statements and scientific opinions disagree about the clinical usefulness. OBJECTIVE: : A World Allergy Organization Special Committee on Food Allergy and Nutrition review of the evidence regarding the use of probiotics for the prevention and treatment of allergy. METHODS: : A qualitative and narrative review of the literature on probiotic treatment of allergic disease was carried out to address the diversity and variable quality of relevant studies. This variability precluded systematization, and an expert panel group discussion method was used to evaluate the literature. In the absence of systematic reviews of treatment, meta-analyses of prevention studies were used to provide data in support of probiotic applications. RESULTS: : Despite the plethora of literature, probiotic research is still in its infancy. There is a need for basic microbiology research on the resident human microbiota. Mechanistic studies from biology, immunology, and genetics are needed before we can claim to harness the potential of immune modulatory effects of microbiota. Meanwhile, clinicians must take a step back and try to link disease state with alterations of the microbiota through well-controlled long-term studies to identify clinical indications. CONCLUSIONS: : Probiotics do not have an established role in the prevention or treatment of allergy. No single probiotic supplement or class of supplements has been demonstrated to efficiently influence the course of any allergic manifestation or long-term disease or to be sufficient to do so. Further epidemiologic, immunologic, microbiologic, genetic, and clinical studies are necessary to determine whether probiotic supplements will be useful in preventing allergy. Until then, supplementation with probiotics remains empirical in allergy medicine. In the future, basic research should focus on homoeostatic studies, and clinical research should focus on preventive medicine applications, not only in allergy. Collaborations between allergo-immunologists and microbiologists in basic research and a multidisciplinary approach in clinical research are likely to be the most fruitful.
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    Probiotics to improve outcomes of colic in the community: Protocol for the Baby Biotics randomised controlled trial
    Sung, V ; Hiscock, H ; Tang, M ; Mensah, FK ; Heine, RG ; Stock, A ; York, E ; Barr, RG ; Wake, M (BMC, 2012-08-29)
    BACKGROUND: Infant colic, characterised by excessive crying/fussing for no apparent cause, affects up to 20% of infants under three months of age and is a great burden to families, health professionals and the health system. One promising approach to improving its management is the use of oral probiotics. The Baby Biotics trial aims to determine whether the probiotic Lactobacillus reuteri DSM 17938 is effective in reducing crying in infants less than threeā€‰months old (<13.0ā€‰weeks) with infant colic when compared to placebo. DESIGN: Double-blind, placebo-controlled randomised trial in Melbourne, Australia. PARTICIPANTS: 160 breast and formula fed infants less than threeā€‰months old who present either to clinical or community services and meet Wessel's criteria of crying and/or fussing. INTERVENTION: Oral once-daily Lactobacillus reuteri (1x108 cfu) versus placebo for oneā€‰month. PRIMARY OUTCOME: Infant crying/fussing time per 24ā€‰hours at oneā€‰month. SECONDARY OUTCOMES: i) number of episodes of infant crying/fussing per 24ā€‰hours and ii) infant sleep duration per 24ā€‰hours (at 7, 14, 21, 28ā€‰days and 6ā€‰months); iii) maternal mental health scores, iv) family functioning scores, v) parent quality adjusted life years scores, and vi) intervention cost-effectiveness (at one and sixā€‰months); and vii) infant faecal microbiota diversity, viii) infant faecal calprotectin levels and ix) Eschericia coli load (at oneā€‰month only). ANALYSIS: Primary and secondary outcomes for the intervention versus control groups will be compared with t tests and non-parametric tests for continuous data and chi squared tests for dichotomous data. Regression models will be used to adjust for potential confounding factors. Intention-to-treat analysis will be applied. DISCUSSION: An effective, practical and acceptable intervention for infant colic would represent a major clinical advance. Because our trial includes breast and formula-fed babies, our results should generalise to most babies with colic. If cost-effective, the intervention's simplicity is such that it could be widely taken up as a new standard of care in the primary and secondary care sectors. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95287767.
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    Lactose intolerance and gastrointestinal cow's milk allergy in infants and children - common misconceptions revisited
    Heine, RG ; AlRefaee, F ; Bachina, P ; De Leon, JC ; Geng, L ; Gong, S ; Armando Madrazo, J ; Ngamphaiboon, J ; Ong, C ; Rogacion, JM (ELSEVIER SCIENCE BV, 2017-12-12)
    Lactose is the main carbohydrate in human and mammalian milk. Lactose requires enzymatic hydrolysis by lactase into D-glucose and D-galactose before it can be absorbed. Term infants express sufficient lactase to digest about one liter of breast milk daily. Physiological lactose malabsorption in infancy confers beneficial prebiotic effects, including the establishment of Bifidobacterium-rich fecal microbiota. In many populations, lactase levels decline after weaning (lactase non-persistence; LNP). LNP affects about 70% of the world's population and is the physiological basis for primary lactose intolerance (LI). Persistence of lactase beyond infancy is linked to several single nucleotide polymorphisms in the lactase gene promoter region on chromosome 2. Primary LI generally does not manifest clinically before 5 years of age. LI in young children is typically caused by underlying gut conditions, such as viral gastroenteritis, giardiasis, cow's milk enteropathy, celiac disease or Crohn's disease. Therefore, LI in childhood is mostly transient and improves with resolution of the underlying pathology. There is ongoing confusion between LI and cow's milk allergy (CMA) which still leads to misdiagnosis and inappropriate dietary management. In addition, perceived LI may cause unnecessary milk restriction and adverse nutritional outcomes. The treatment of LI involves the reduction, but not complete elimination, of lactose-containing foods. By contrast, breastfed infants with suspected CMA should undergo a trial of a strict cow's milk protein-free maternal elimination diet. If the infant is not breastfed, an extensively hydrolyzed or amino acid-based formula and strict cow's milk avoidance are the standard treatment for CMA. The majority of infants with CMA can tolerate lactose, except when an enteropathy with secondary lactase deficiency is present.
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    Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP-an international interpretation of the MAP (Milk Allergy in Primary Care) guideline
    Venter, C ; Brown, T ; Meyer, R ; Walsh, J ; Shah, N ; Nowak-Wegrzyn, A ; Chen, T-X ; Fleischer, DM ; Heine, RG ; Levin, M ; Vieira, MC ; Fox, AT (BIOMED CENTRAL LTD, 2017-08-23)
    Cow's milk allergy (CMA) is one of the most common presentations of food allergy seen in early childhood. It is also one of the most complex food allergies, being implicated in IgE-mediated food allergy as well as diverse manifestations of non-IgE-mediated food allergy. For example, gastrointestinal CMA may present as food protein induced enteropathy, enterocolitis or proctocolitis. Concerns regarding the early and timely diagnosis of CMA have been highlighted over the years. In response to these, guideline papers from the United Kingdom (UK), Australia, Europe, the Americas and the World Allergy Organisation have been published. The UK guideline, 'Diagnosis and management of non-IgE-mediated cow's milk allergy in infancy-a UK primary care practical guide' was published in this journal in 2013. This Milk Allergy in Primary Care (MAP) guideline outlines in simple algorithmic form, both the varying presentations of cow's milk allergy and also focuses on the practical management of the most common presentation, namely mild-to-moderate non-IgE-mediated allergy. Based on the international uptake of the MAP guideline, it became clear that there was a need for practical guidance beyond the UK. Consequently, this paper presents an international interpretation of the MAP guideline to help practitioners in primary care settings around the world. It incorporates further published UK guidance, feedback from UK healthcare professionals and affected families and, importantly, also international guidance and expertise.
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    Eosinophilic Oesophagitis
    ALLEN, K ; Heine, R ; Ebisawa, M ; Ballmer-Weber, BK ; Vieths, S ; Wood, RA (Karger, 2015)
    Featuring contributions by world-renowned experts, this book presents the current concept, practice and recent advances in the field of food allergy.
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    Proximal and distal gastro-oesophageal reflux in chronic obstructive pulmonary disease and bronchiectasis
    Lee, AL ; Button, BM ; Denehy, L ; Roberts, SJ ; Bamford, TL ; Ellis, SJ ; Mu, F-T ; Heine, RG ; Stirling, RG ; Wilson, JW (WILEY, 2014-02)
    BACKGROUND AND OBJECTIVE: The aims of this observational study were (i) to examine the prevalence of symptomatic and clinically silent proximal and distal gastro-oesophageal reflux (GOR) in adults with chronic obstructive pulmonary disease (COPD) or bronchiectasis, (ii) the presence of gastric aspiration, and (iii) to explore the possible clinical significance of this comorbidity in these conditions. METHODS: Twenty-seven participants with COPD, 27 with bronchiectasis and 17 control subjects completed reflux symptom evaluation and dual-channel 24ā€‰h oesophageal pH monitoring. In those with lung disease, pepsin levels in sputum samples were measured using enzyme-linked immunosorbent assay, with disease severity (lung function and high-resolution computed tomography) also measured. RESULTS: The prevalence of GOR in COPD was 37%, in bronchiectasis was 40% and in control subjects was 18% (Pā€‰=ā€‰0.005). Of those diagnosed with GOR, clinically silent reflux was detected in 20% of participants with COPD and 42% with bronchiectasis. While pepsin was found in 33% of COPD and 26% of bronchiectasis participants, the presence of pepsin in sputum was not related to a diagnosis of GOR based on oesophageal pH monitoring in either condition. Neither a diagnosis of GOR nor the presence of pepsin was associated with increased severity of lung disease in COPD or bronchiectasis. CONCLUSIONS: The prevalence of GOR in COPD or bronchiectasis is twice that of the control population, and the diagnosis could not be based on symptoms alone. Pepsin was detected in sputum in COPD and bronchiectasis, suggesting a possible role of pulmonary aspiration, which requires further exploration.