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      Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood

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          <div class="section"> <a class="named-anchor" id="ab-poi180013-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e297">Question</h5> <p id="d5534818e299">Does use of medications that disturb the microbiome in infancy increase subsequent risk of developing allergic diseases? </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e302">Findings</h5> <p id="d5534818e304">In this cohort study of 792 130 children, the hazard of developing an allergic disease was significantly increased in those who had received acid-suppressive medications or antibiotics during the first 6 months of life. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e307">Meaning</h5> <p id="d5534818e309">Exposure to acid-suppressive medications or antibiotics in the first 6 months of life may increase risk of allergic disease development. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e313">Importance</h5> <p id="d5534818e315">Allergic diseases are prevalent in childhood. Early exposure to medications that can alter the microbiome, including acid-suppressive medications and antibiotics, may influence the likelihood of allergy. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e318">Objective</h5> <p id="d5534818e320">To determine whether there is an association between the use of acid-suppressive medications or antibiotics in the first 6 months of infancy and development of allergic diseases in early childhood. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e323">Design, Setting, and Participants</h5> <p id="d5534818e325">A retrospective cohort study was conducted in 792 130 children who were Department of Defense TRICARE beneficiaries with a birth medical record in the Military Health System database between October 1, 2001, and September 30, 2013, with continued enrollment from within 35 days of birth until at least age 1 year. Children who had an initial birth stay of greater than 7 days or were diagnosed with any of the outcome allergic conditions within the first 6 months of life were excluded from the study. Data analysis was performed from April 15, 2015, to January 4, 2018. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e328">Exposures</h5> <p id="d5534818e330">Exposures were defined as having any dispensed prescription for a histamine-2 receptor antagonist (H <sub>2</sub>RA), proton pump inhibitor (PPI), or antibiotic. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e336">Main Outcomes and Measures</h5> <p id="d5534818e338">The main outcome was allergic disease, defined as the presence of food allergy, anaphylaxis, asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, urticaria, contact dermatitis, medication allergy, or other allergy. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e341">Results</h5> <p id="d5534818e343">Of 792 130 children (395 215 [49.9%] girls) included for analysis, 60 209 (7.6%) were prescribed an H <sub>2</sub>RA, 13 687 (1.7%) were prescribed a PPI, and 131 708 (16.6%) were prescribed an antibiotic during the first 6 months of life. Data for each child were available for a median of 4.6 years. Adjusted hazard ratios (aHRs) in children prescribed H <sub>2</sub>RAs and PPIs, respectively, were 2.18 (95% CI, 2.04-2.33) and 2.59 (95% CI, 2.25-3.00) for food allergy, 1.70 (95% CI, 1.60-1.80) and 1.84 (95% CI, 1.56-2.17) for medication allergy, 1.51 (95% CI, 1.38-1.66) and 1.45 (95% CI, 1.22-1.73) for anaphylaxis, 1.50 (95% CI, 1.46-1.54) and 1.44 (95% CI, 1.36-1.52) for allergic rhinitis, and 1.25 (95% CI, 1.21-1.29) and 1.41 (95% CI, 1.31-1.52) for asthma. The aHRs after antibiotic prescription in the first 6 months of life were 2.09 (95% CI, 2.05-2.13) for asthma, 1.75 (95% CI, 1.72-1.78) for allergic rhinitis, 1.51 (95% CI, 1.38-1.66) for anaphylaxis, and 1.42 (95% CI, 1.34-1.50) for allergic conjunctivitis. </p> </div><div class="section"> <a class="named-anchor" id="ab-poi180013-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d5534818e352">Conclusions and Relevance</h5> <p id="d5534818e354">This study found associations between the use of acid-suppressive medications and antibiotics during the first 6 months of infancy and subsequent development of allergic disease. Acid-suppressive medications and antibiotics should be used during infancy only in situations of clear clinical benefit. </p> </div><p class="first" id="d5534818e357">This cohort study examines the association between development of childhood allergies and use of histamine-2 receptor antagonists, proton pump inhibitors, or antibiotics during infancy. </p>

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          Commensal bacteria protect against food allergen sensitization.

          Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.
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            The allergy epidemics: 1870-2010.

            Before the first description of hay fever in 1870, there was very little awareness of allergic disease, which is actually similar to the situation in prehygiene villages in Africa today. The best explanation for the appearance and subsequent increase in hay fever at that time is the combination of hygiene and increased pollen secondary to changes in agriculture. However, it is important to remember that the major changes in hygiene in Northern Europe and the United States were complete by 1920. Asthma in children did not start to increase until 1960, but by 1990, it had clearly increased to epidemic numbers in all countries where children had adopted an indoor lifestyle. There are many features of the move indoors that could have played a role; these include increased sensitization to indoor allergens, diet, and decreased physical activity, as well as the effects of prolonged periods of shallow breathing. Since 1990, there has been a remarkable increase in food allergy, which has now reached epidemic numbers. Peanut has played a major role in the food epidemic, and there is increasing evidence that sensitization to peanut can occur through the skin. This suggests the possibility that changes in lifestyle in the last 20 years could have influenced the permeability of the skin. Overall, the important conclusion is that sequential changes in lifestyle have led to increases in different forms of allergic disease. Equally, it is clear that the consequences of hygiene, indoor entertainment, and changes in diet or physical activity have never been predicted.
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              Food allergy among children in the United States.

              The goals were to estimate the prevalence of food allergy and to describe trends in food allergy prevalence and health care use among US children. A cross-sectional survey of data on food allergy among children <18 years of age, as reported in the 1997-2007 National Health Interview Survey, 2005-2006 National Health and Nutrition Examination Survey, 1993-2006 National Hospital Ambulatory Medical Care Survey and National Ambulatory Medical Care Survey, and 1998-2006 National Hospital Discharge Survey, was performed. Reported food allergies, serum immunoglobulin E antibody levels for specific foods, ambulatory care visits, and hospitalizations were assessed. In 2007, 3.9% of US children <18 years of age had reported food allergy. The prevalence of reported food allergy increased 18% (z = 3.4; P < .01) from 1997 through 2007. In 2005-2006, serum immunoglobulin E antibodies to peanut were detectable for an estimated 9% of US children. Ambulatory care visits tripled between 1993 and 2006 (P < .01). From 2003 through 2006, an estimated average of 317000 food allergy-related, ambulatory care visits per year (95% confidence interval: 195000-438000 visits per year) to emergency and outpatient departments and physician's offices were reported. Hospitalizations with any recorded diagnoses related to food allergy also increased between 1998-2000 and 2004-2006, from an average of 2600 discharges per year to 9500 discharges per year (z = 3.4; P < .01), possibly because of increased use of food allergy V codes. Several national health surveys indicate that food allergy prevalence and/or awareness has increased among US children in recent years.

                Author and article information

                JAMA Pediatrics
                JAMA Pediatr
                American Medical Association (AMA)
                June 01 2018
                June 04 2018
                : 172
                : 6
                : e180315
                [1 ]Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland
                [2 ]Department of Pediatrics, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland
                [3 ]Division of Allergy and Immunology, Department of Medicine, Dwight D. Eisenhower Army Medical Center, Ft Gordon, Georgia
                © 2018


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