Article

Relationship between treatment with antacid medication and the prevalence of food allergy in children

Authors:
  • Epidemiology Centre
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Abstract

Food allergy affects 8% of preschool children, but factors responsible for food allergy in children are poorly understood. Use of antacid medication may be a contributing factor. The purpose of this study was to determine if parent-reported antacid medication use was associated with higher prevalence of food allergy in atopic children. In this cross-sectional study, parents of children with atopic diseases completed a questionnaire relating to a history of treatment with antacid medication and food allergy. Charts were independently reviewed for food-specific IgE and/or skin-prick test results. Food allergy was defined as a reaction to a food consistent with the anaphylaxis consensus statement and either an elevated food-specific IgE or a positive food skin-prick test. One hundred four questionnaires were completed. Mean age of the participating children was 7.0 ± 4.3 years (range, 5 months to 18 years of age). Forty-seven (45%) individuals were reported to have taken an antacid medication in the past. History of taking antacid medication was associated with an increased prevalence (57% (27)/47 versus 32% (18)/57) and higher prevalence of food allergy of having food allergy (aPR, 1.7 [1.1-2.5]). Mean peanut food-specific IgE was higher in those with a history of taking antacid medication (11.0 ± 5.0 versus 2.0 ± 5.5.; p = 0.01). History of treatment with antacid medication is associated with an increased prevalence of having food allergy.

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... In a cross-sectional study examining children in an allergy clinic, DeMuth et al found that history of taking antacid medication in children according to parental report was associated with an increased prevalence of food allergy. 60 This may be explained by the effects of antacids on gastric pH and subsequent influence on the digestion of proteins. ...
Article
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Article
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... Lastly, several external subverters capable of indirectly perturbing the internal milieu may establish conditions conducive to allergic sensitization. For example, bacterial exposure early in life, antibiotic and antacid abuse during infancy, or birth through caesarean section have been associated with increased prevalence of food allergy, presumably a result of alterations to the homeostatic microbiota [135][136][137][138][139]. ...
Article
Full-text available
In contrast with Th1 immune responses against pathogenic viruses and bacteria, the incipient events that generate Th2 responses remain less understood. One difficulty in the identification of universal operating principles stems from the diversity of entities against which cellular and molecular Th2 responses are produced. Such responses are launched against harmful macroscopic parasites and noxious substances, such as venoms, but also against largely innocuous allergens. This suggests that the established understanding about sense and recognition applied to Th1 responses may not be translatable to Th2 responses. This review will discuss processes and signals known to occur in Th2 responses, particularly in the context of food allergy. We propose that perturbations of homeostasis at barrier sites induced by external or internal subverters, which can activate or lower the threshold activation of the immune system, are the major requirement for allergic sensitization. Innate signals produced in the tissue under these conditions equip dendritic cells with a program that forms an adaptive Th2 response.
... 57 Also, for pediatric patients, an impact of drug-induced gastric acid suppression on food allergy development was reported. 61,62 Even during pregnancy, maternal anti-ulcer drug intake was found to be associated with a higher risk for childhood allergy development. [63][64][65] Additionally, in patients with diagnosed food allergies, a functional gastric protein digestion is of relevance. ...
Article
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... Moreover, for aged patients living in a geriatric nursing home, the intake of anti-ulcer drugs was found to be associated with a significant shift of the immune response towards a type 2-environment [114]. Not only in elderly, but also in pediatric patients, anti-ulcer drug intake was reported to be associated with the development of food allergy [115,116]. In line, a recent cohort study of 792,130 children demonstrated a higher allergy risk for children being treated with either antibiotics or acid-suppressive medication during the first 6 months of life [7]. ...
Article
Full-text available
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... Additionally, murine as well as human studies confirmed the association between hypoacidic gastric pH due to medication with gastric acid suppressive drugs and food allergy development [8][9][10]12,13]. These data were confirmed by other groups reporting food allergy development after intake of anti-ulcer drugs such as proton pump inhibitors (PPIs) also in the pediatric population in large cohort studies [14][15][16]. Moreover, in a study with fish allergic patients we confirmed the protective role of gastric digestion in an already-established food allergy [17]. ...
Article
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Food allergy represents an increasing health concern worldwide. To identify mechanisms and risk factors associated with the development of food allergy, major research efforts are ongoing. For a long time, only food allergens that are resistant to gastric enzymes were believed to have sensitizing capacity via the oral route. However, in recent years several studies reported that even important food allergens can be readily degraded by digestive enzymes. Interestingly, a number of in vitro experiments have confirmed that by elevating gastric pH levels, the resulting reduction of physiological gastric digestion was associated with protein resistance. Additionally, pharmacological gastric acid suppression was found to be a risk factor for the induction of food allergy. In contrast, protein modifications resulting in increased susceptibility to digestive enzymes were reported to decrease the sensitizing capacity of these proteins via the oral route. The data reviewed here highlight the important gate-keeping function of physiological gastric digestion in food allergy.
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Proton pump inhibitors are considered to be highly selective and effective drugs, which have few side effects. They are used in both adults and children (including infants) as well as in pregnant women. By increasing the gastric fluid pH, they impair the activation process and reduce the secretion of pepsin, secretin and pancreatic proteases, thereby impairing protein degradation. The remaining peptides are immunoreactive and lead to the development of an allergic response, while the increased permeability of the gastrointestinal tract mucosa may also induce sensitization. Observational studies conducted in patients with gastroenterological disorders, children with allergy diseases and experimental studies in animals have demonstrated that the use of anti-ulcer drugs favours sensitization to selected food allergens.
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Recently, we have demonstrated that anti-ulcer drugs, such as H2-receptor blockers and proton pump inhibitors, promote the development of immediate type food allergy toward digestion-labile proteins in mice. The aim of this study was to examine the allergological relevance of these findings in humans. In an observational cohort study, we screened 152 adult patients from a gastroenterological outpatient clinic with negative case histories for atopy or allergy, who were medicated with H2-receptor blockers or proton pump inhibitors for 3 months. IgE reactivities to food allergens before and after 3 months of anti-acid treatment were compared serologically. Ten percent of the patients showed a boost of preexisting IgE antibodies and 15% de novo IgE formation toward numerous digestion-labile dietary compounds, like milk, potato, celery, carrots, apple, orange, wheat, and rye flour. Thus, the relative risk to develop food-specific IgE after anti-acid therapy was 10.5 (95% confidence interval: 1.44-76.48). The long-term effect was evaluated 5 months after therapy. Food-specific IgE could still be measured in 6% of the patients, as well as significantly elevated serum concentrations of ST2, a Th2-specific marker. An unspecific boost during the pollen season could be excluded, as 50 untreated control patients revealed no changes in their IgE pattern. In line with our previous animal experiments, our data strongly suggest that anti-ulcer treatment primes the development of IgE toward dietary compounds in long-term acid-suppressed patients.
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Objective To update the findings of the 2005 systematic review of population-based studies assessing the epidemiology of gastro-oesophageal reflux disease (GERD). Design PubMed and Embase were screened for new references using the original search strings. Studies were required to be population-based, to include ≥200 individuals, to have response rates ≥50% and recall periods <12 months. GERD was defined as heartburn and/or regurgitation on at least 1 day a week, or according to the Montreal definition, or diagnosed by a clinician. Temporal and geographic trends in disease prevalence were examined using a Poisson regression model. Results 16 studies of GERD epidemiology published since the original review were found to be suitable for inclusion (15 reporting prevalence and one reporting incidence), and were added to the 13 prevalence and two incidence studies found previously. The range of GERD prevalence estimates was 18.1%–27.8% in North America, 8.8%–25.9% in Europe, 2.5%–7.8% in East Asia, 8.7%–33.1% in the Middle East, 11.6% in Australia and 23.0% in South America. Incidence per 1000 person-years was approximately 5 in the overall UK and US populations, and 0.84 in paediatric patients aged 1–17 years in the UK. Evidence suggests an increase in GERD prevalence since 1995 (p<0.0001), particularly in North America and East Asia. Conclusions GERD is prevalent worldwide, and disease burden may be increasing. Prevalence estimates show considerable geographic variation, but only East Asia shows estimates consistently lower than 10%.
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These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, or the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
Histamine plays an important role in allergy mainly through histamine H1 receptor (H1R). Recent studies showed that the H1R level is elevated in allergic conditions, suggesting that this will make the allergic symptoms worse by intensifying H1R-mediated processes. Some cytokines are also involved in allergy, and interleukin-4 (IL-4) has been implicated as an important mediator of allergic inflammation. It is noteworthy that the level of IL-4 is elevated under allergic states. We tested whether IL-4 has a role in up-regulating H1R level by using the cultured human HeLa cell as a model system that expresses both IL-4 receptor and H1R. IL-4 stimulation increased H1R protein levels and H1R mRNA levels. IL-4 also increased H1R promoter activity, but had no effect on H1R mRNA stability, indicating that up-regulation of H1R was due to an increase in H1R mRNA synthesis. IL-4 activated STAT6 (signal transducer and activator of transcription 6) in HeLa cells, and up-regulation of H1R mRNA and activation of STAT6 by IL-4 were inhibited by a specific JAK3 (Janus-activated kinase 3) inhibitor. Stimulation with histamine also up-regulated H1R mRNA, and co-stimulation with histamine and IL-4 elevated H1R mRNA level significantly higher than the stimulation with histamine or IL-4 alone did. These results indicated that IL-4 up-regulated H1R mRNA level through increased transcription of H1R gene via JAK3-STAT6 pathway. The effects of histamine and IL-4 were additive, suggesting that these allergic mediators will work together to up-regulate H1R level, and thus make the allergic symptom worse by intensifying H1R-mediated allergic processes.
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Oral food challenges are procedures conducted by allergists/immunologists to make an accurate diagnosis of immediate, and occasionally delayed, adverse reactions to foods. The timing of the challenge is carefully chosen based on the individual patient history and the results of skin prick tests and food specific serum IgE values. The type of the challenge is determined by the history, the age of the patient, and the likelihood of encountering subjective reactions. The food challenge requires preparation of the patient for the procedure and preparation of the office for the organized conduct of the challenge, for a careful assessment of the symptoms and signs and the treatment of reactions. The starting dose, the escalation of the dosing, and the intervals between doses are determined based on experience and the patient's history. The interpretation of the results of the challenge and arrangements for follow-up after a challenge are important. A negative oral food challenge result allows introduction of the food into the diet, whereas a positive oral food challenge result provides a sound basis for continued avoidance of the food.
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Animal models are essential for analyzing the allergenic potential of food proteins and for investigating mechanisms underlying food allergy. Based on previous studies revealing acid-suppression medication as risk factor for food allergy induction, we aimed to establish a mouse model mimicking the natural route of sensitization in patients. The effect of acid-suppressing medication on murine gastric pH was assessed by intragastric pH measurements after two injections of a proton pump inhibitor (PPI). To investigate dose-dependency, mice were fed different concentrations of ovalbumin (OVA; 0.2, 0.5, 1.0, 2.5 or 5.0mg) either with or without anti-ulcer medication. Additionally, different routes of exposure (i.p. vs. oral) were compared in a second immunization experiment. Sera were screened for OVA-specific antibody titers (IgG1, IgG2a and IgE) in ELISA and RBL assay. Clinical reactivity was evaluated by measuring rectal temperature after oral challenge and by type I skin tests. Two intravenous injections of PPI significantly elevated the gastric pH from 2.97 to 5.3. Only oral immunization with 0.2mg OVA under anti-acid medication rendered elevated IgG1, IgG2a and IgE titers compared to all other concentrations. Protein feeding alone altered antibody titers only marginally. Even though also i.p. immunizations induced high levels of specific IgE, only oral immunizations under anti-acids induced anaphylactic reactions evidenced by a significant decrease of body temperature. Only low-dosage ovalbumin feedings under anti-acid medication resulted in IgE mediated food allergy. Based on this knowledge we have established a suitable food allergy model for further investigations of food adverse reactions.
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Up to 8% of children less than 3 years of age and approximately 2% of the adult population experience food-induced allergic disorders. A limited number of foods are responsible for the vast majority of food-induced allergic reactions: milk, egg, peanuts, fish, and tree nuts in children and peanuts, tree nuts, fish, and shellfish in adults. Food-induced allergic reactions are responsible for a variety of symptoms involving the skin, gastrointestinal tract, and respiratory tract and may be caused by IgE-mediated and non-IgE-mediated mechanisms. In part 1 of this series, immunopathogenic mechanisms and clinical disorders of food allergy are described.
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Awareness of the clinical features of anaphylaxis and its causative triggers is important if recurrent episodes are to be avoided. The incidence of anaphylaxis in the general population is often underreported, and epidemiologic studies are few. Because an accurate profile of anaphylaxis could heighten awareness of this problem, we investigated the epidemiology of anaphylaxis in the general population of Olmsted County, Minn. The purpose of this study was to describe the epidemiology of anaphylaxis in Olmsted County residents from 1983 through 1987. This was a retrospective population-based cohort study. The medical records of 1255 Olmsted County residents identified by computer-linked, medical diagnostic indices (the Rochester Epidemiology Study) were reviewed retrospectively to identify residents whose clinical episodes met the criteria for anaphylaxis. We determined the incidence and rate of occurrence of anaphylaxis, rate of recurrence, prevalence of atopy, cause of anaphylaxis, frequency of referral to an allergy specialist, hospital admission rate, and case-fatality rate. There were 133 residents who experienced 154 anaphylactic episodes during the 5-year period: 116 residents had 1 episode of anaphylaxis, 13 residents had 2 episodes, and 4 residents had 3 episodes. The anaphylaxis occurrence rate was 30 per 100,000 person-years (95% confidence interval, 25-35). There were 110 residents who had a first lifetime episode of anaphylaxis (that was medically evaluated) during the years 1983 to 1987. The average annual incidence rate of anaphylaxis was 21 per 100,000 person-years (95% confidence interval, 17-25). Atopy was present in 53% of the cohort, and allergy consultation was obtained in 52%. A suspect allergen was identified in 68% of the cohort, most frequently a food, medication, or insect sting. The hospitalization rate was 7%, and 1 patient died. The incidence of anaphylaxis is less than 1%, and death rarely occurs. People with atopy experience anaphylaxis more frequently than people without atopy. Anaphylaxis frequently is not recognized by patients and physicians.
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Digestible proteins were supposed to be irrelevant for oral sensitization and induction of food allergy. Approximately 10% of the adult population uses antacids for the treatment of dyspeptic disorders, drugs that hinder peptic digestion. In these patients, proteins that are normally degradable might act as food allergens. We aimed to study the influence of antacid intake on the allergenicity of dietary proteins, taking sturgeon caviar and parvalbumin, the major fish allergen, as examples. Caviar proteins and recombinant parvalbumin from carp, rCyp c 1, were applied for intragastric feedings with or without the antacids sucralfate, ranitidine or omeprazole, using a Balb/c mouse model. Both caviar proteins and parvalbumin were rapidly degraded in an in vitro digestion assay at pH 2.0, but not at pH 5.0, imitating the effect of antacids. The groups fed with caviar in combination with ranitidine hydrochloride intramuscularly or sucralfate orally had significant levels of caviar-specific IgE antibodies (P <.01), T-cell reactivity, and elevated counts of gastrointestinal eosinophils and mast cells. Food allergy in these groups was further evidenced by oral provocation tests and positive immediate-type skin reactivity. In contrast, feedings with caviar alone led to antigen-specific T-cell tolerance. None of the groups showed immune reactivity against the daily mouse diet. As a proof of the principle, feeding mice with parvalbumin in combination with ranitidine or omeprazole intramuscularly induced allergen-specific IgE antibodies (P <.05). When antacid medication impairs the gastric digestion, IgE synthesis toward novel dietary proteins is promoted, leading to food allergy.
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Vaccination represents one of the most efficacious and cost-effective medical interventions. It is the only medical intervention proven to eliminate disease at a global level. Many of the pathogens against which we most require adequate vaccines infect via the highly exposed mucosal surfaces. For this reason the mucosa is often considered the first, and sometimes only, line of defense. Therefore, responses that protect the local mucosa are vital. In this review, we first explore the immunological mechanisms that protect the mucosa. We then review the literature of mucosal vaccines within the principles of antigenic composition, dose, and danger, highlighting the need and niche for the next generation of mucosal vaccines.
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Histamine receptors play an important role in the pathogenesis of nasal allergy. Activation of histamine receptor 1 (H1R) and 2 (H2R) can cause allergic symptoms which can be blocked effectively by antihistamines. H1R and H2R transcript levels have been found to be up-regulated in perennial - but not in seasonal - allergic rhinitis (AR). The present study aimed to explore H1R and H2R expression in complex tissues of the nasal mucosa of perennial allergic rhinitis (PAR). Ten patients with PAR and 13 non-AR subjects were recruited for the study by medical history, physical examination and laboratory screening tests. In this study, we have analysed single cells dissected from the nasal mucosa biopsies by laser-assisted microdissection. H1R mRNA expression was analysed in different cell types such as epithelial, endothelial, mucus and inflammatory cells isolated from the nasal mucosa of PAR in comparison with non-AR subjects. H1R mRNA gene expression level was significantly increased in the nasal mucosa of PAR in comparison with non-AR (P<0.0001). H1R mRNA was significantly elevated in epithelial (P<0.001) and mucus cells (P<0.05) of PAR in comparison with non-AR whereas H1R gene expression levels in endothelial cells between both groups were not changed (P=0.23). Interestingly, inflammatory cells in the nasal mucosa of PAR patients were also strongly expressed H1R mRNA (P<0.001). The present study indicates that PAR alters the expression of H1R mRNA in epithelial, mucus and inflammatory cells of the nasal mucosa and but not in endothelial cells. Therefore, epithelial, mucus and inflammatory cells may play an important role in histamine-mediated allergic airway inflammation in PAR.
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In addition to its well-characterized effects in the acute allergic inflammatory responses, histamine has been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. Histamine can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization, and other functions leading to chronic inflammation. Histamine also regulates dendritic cells, T cells and B cells, as well as related antibody isotype responses. In addition, acting through its receptor 2, histamine positively interferes with the peripheral antigen tolerance induced by T regulatory cells in several pathways. The diverse effects of histamine on immune regulation appear to be due to differential expression and regulation of 4 types of histamine receptors and their distinct intracellular signals. In addition, differences in affinities of these receptors for histamine is highly decisive for the biological effects of histamine and drugs that target histamine receptors. This article highlights recent discoveries in histamine immunobiology and discusses their relevance in allergic inflammation.
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Peanut allergy has become a major health concern worldwide, especially in developed countries. However, the reasons for this increasing prevalence over the past several decades are not well understood. Because of the potentially severe health consequences of peanut allergy, those suspected of having had an allergic reaction to peanuts deserve a thorough evaluation. All patients with peanut allergy should be given an emergency management plan, as well as epinephrine and antihistamines to have on hand at all times. Patients and families should be taught to recognise early allergic reactions to peanuts and how to implement appropriate peanut-avoidance strategies. It is imperative that severe, or potentially severe, reactions be treated promptly with intramuscular epinephrine and oral antihistamines. Patients who have had such a reaction should be kept under observation in a hospital emergency department or equivalent for up to 4 h because of the possible development of the late-phase allergic response. This Seminar looks at the changing epidemiology of this allergy--and theories as to the rise in prevalence, diagnosis, and management of the allergy, and potential new treatments and prevention strategies under development.