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      Prevention of New Respiratory Episodes in Children with Recurrent Respiratory Infections: An Expert Consensus Statement from the World Association of Infectious Diseases and Immunological Disorders (WAidid)

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          Abstract

          In healthy infants and young children, the development of respiratory tract infections (RTIs) is extremely common. In this paper, we present an international consensus of the available approaches for the prevention of recurrent RTIs in children, including the atopic/allergic ones as well as those with asthma. Few convincing measures for reducing the frequency and clinical relevance of recurrent respiratory episodes in RTI-prone children have been developed until now. Among the most recently suggested measures, immunotherapy is attractive, but only for OM-85 is there a sufficient number of well-conducted clinical trials confirming efficacy in RTIs prevention with an adequate safety profile. In the case of probiotics, it is not clear which bacteria can offer the best results and which dosage and schedule of administration are the most effective. The problems of dosage and the schedule of administration are not solved also for vitamin D, despite some promising efficacy results. While we wait for new knowledge, the elimination or reduction as much as possible of the environmental factors that favor RTIs, vaccination when available and/or indicated, and the systematic application of the traditional methods for infection prevention, such as hand washing, remain the best measures to prevent recurrent infections in RTI-prone children.

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          Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic.

          An expert panel was convened in October 2013 by the International Scientific Association for Probiotics and Prebiotics (ISAPP) to discuss the field of probiotics. It is now 13 years since the definition of probiotics and 12 years after guidelines were published for regulators, scientists and industry by the Food and Agriculture Organization of the United Nations and the WHO (FAO/WHO). The FAO/WHO definition of a probiotic--"live microorganisms which when administered in adequate amounts confer a health benefit on the host"--was reinforced as relevant and sufficiently accommodating for current and anticipated applications. However, inconsistencies between the FAO/WHO Expert Consultation Report and the FAO/WHO Guidelines were clarified to take into account advances in science and applications. A more precise use of the term 'probiotic' will be useful to guide clinicians and consumers in differentiating the diverse products on the market. This document represents the conclusions of the ISAPP consensus meeting on the appropriate use and scope of the term probiotic.
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            Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data

            Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect. Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015. Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome. Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality. Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit. Systematic review registration PROSPERO CRD42014013953.
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              Dysbiosis of the gut microbiota in disease

              There is growing evidence that dysbiosis of the gut microbiota is associated with the pathogenesis of both intestinal and extra-intestinal disorders. Intestinal disorders include inflammatory bowel disease, irritable bowel syndrome (IBS), and coeliac disease, while extra-intestinal disorders include allergy, asthma, metabolic syndrome, cardiovascular disease, and obesity. In many of these conditions, the mechanisms leading to disease development involves the pivotal mutualistic relationship between the colonic microbiota, their metabolic products, and the host immune system. The establishment of a ‘healthy’ relationship early in life appears to be critical to maintaining intestinal homeostasis. Whilst we do not yet have a clear understanding of what constitutes a ‘healthy’ colonic microbiota, a picture is emerging from many recent studies identifying particular bacterial species associated with a healthy microbiota. In particular, the bacterial species residing within the mucus layer of the colon, either through direct contact with host cells, or through indirect communication via bacterial metabolites, may influence whether host cellular homeostasis is maintained or whether inflammatory mechanisms are triggered. In addition to inflammation, there is some evidence that perturbations in the gut microbiota is involved with the development of colorectal cancer. In this case, dysbiosis may not be the most important factor, rather the products of interaction between diet and the microbiome. High-protein diets are thought to result in the production of carcinogenic metabolites from the colonic microbiota that may result in the induction of neoplasia in the colonic epithelium. Ever more sensitive metabolomics methodologies reveal a suite of small molecules produced in the microbiome which mimic or act as neurosignallers or neurotransmitters. Coupled with evidence that probiotic interventions may alter psychological endpoints in both humans and in rodent models, these data suggest that CNS-related co-morbidities frequently associated with GI disease may originate in the intestine as a result of microbial dysbiosis. This review outlines the current evidence showing the extent to which the gut microbiota contributes to the development of disease. Based on evidence to date, we can assess the potential to positively modulate the composition of the colonic microbiota and ameliorate disease activity through bacterial intervention.
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                Author and article information

                Journal
                Microorganisms
                Microorganisms
                microorganisms
                Microorganisms
                MDPI
                2076-2607
                17 November 2020
                November 2020
                : 8
                : 11
                : 1810
                Affiliations
                [1 ]Pediatric Clinic, Pietro Barilla Children’s Hospital, University of Parma, 43126 Parma, Italy
                [2 ]School of Medicine, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre (RS) 90619-900, Brazil; mhjones@ 123456pucrs.br
                [3 ]Department of Pediatric Pneumonology and Allergy, The Medical University of Warsaw, 00-927 Warsaw, Poland; wojciech.feleszko@ 123456wum.edu.pl
                [4 ]Department of Immunology, Universidad Autónoma del Estado de Hidalgo, Pachuca, Hidalgo 42082, Mexico; drortegamartell@ 123456prodigy.net.mx
                [5 ]Faculty of Medicine, Transilvania University, Children’s Clinic Hospital, 500036 Brasov, Romania; oanafp@ 123456yahoo.co.uk
                [6 ]Department of Paediatrics, Sechenov First Moscow State Medical University, 115093 Moscow, Russia; geppe@ 123456mail.ru
                [7 ]Translational Pediatrics and Infectious Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain; federico.martinon.torres@ 123456sergas.es
                [8 ]China National Clinical Research Center for Respiratory Diseases, Department of Respiratory Medicine, Capital Medical University, National Center for Children’s Health, Beijing 100045, China; kunlingshen1717@ 123456163.com
                [9 ]Pulmonary Cell Research and Pneumology, Department of Biomedicine and Internal Medicine, University Hospital Basel, 4002 Basel, Switzerland; michael.roth@ 123456usb.ch
                [10 ]Università degli Studi di Milano, 20122 Milan, Italy; nicola.principi@ 123456unimi.it
                Author notes
                [* ]Correspondence: susanna.esposito@ 123456unimi.it ; Tel.: +39-(05)-21704790
                Author information
                https://orcid.org/0000-0002-8263-1265
                https://orcid.org/0000-0001-6613-2012
                https://orcid.org/0000-0003-1972-6859
                https://orcid.org/0000-0002-9023-581X
                https://orcid.org/0000-0002-8139-2821
                Article
                microorganisms-08-01810
                10.3390/microorganisms8111810
                7698530
                33213053
                02b67f90-a61f-4a68-9db2-4650aa400798
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2020
                : 13 November 2020
                Categories
                Review

                bacterial lysates,pidotimod,probiotics,respiratory infection,respiratory recurrences,vitamin

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