Prostaglandin D2 metabolite in urine is an index of food allergy.

Food allergy is immediate hypersensitive reactions to ingested foods. Since early diagnosis is effective for disease control, development of an objective diagnostic index is required. Using mediator-lipidomics, we found that levels of the urinary prostaglandin D2 (PGD2) metabolite, tetranor-PGDM, reflected the severity of the allergic symptoms and intestinal mast cell hyperplasia in mice. Repeated oral challenges with ovalbumin promoted allergic symptoms in sensitized mice. Particularly, the allergic mice presented with increased numbers of intestinal mast cells, which strongly expressed hematopoietic PGD synthase (H-PGDS). The levels of urinary tetranor-PGDM increased as the disease progressed. Treatment with a mast cell inactivator or an anti-inflammatory steroid attenuated these symptoms and decreased the tetranor-PGDM urinary levels. The levels of urinary tetranor-PGDM did not correlate with the disease severity in murine models of colitis, asthma, or allergic dermatitis. Furthermore, we have shown that urinary levels of tetranor-PGDM were significantly higher in patients with food allergy than those in healthy volunteers and patients with other types of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. These findings suggest that urinary tetranor-PGDM is a useful diagnostic index of food allergy in both mice and humans.

The effect of prenatal exposure to phthalates on food allergy and early eczema in inner-city children.

BACKGROUND AND OBJECTIVE: We hypothesized that maternal prenatal and children urine metabolite concentration of phthalates would be associated with food allergy and early eczema among inner-city children. The study was based on data from the Polish Mother and Child Cohort. METHODS: Prenatal and postnatal exposure to the following phthalates: diethyl phthalate, diisobutyl phthalate, di-n-butyl phthalate, butyl-benzyl phthalate, di(2-ethylhexyl) phthalate, diisononyl phthalate, and di-n-octyl phthalate were determined by measuring phthalate metabolites in the urine collected from the mothers during the third trimester of pregnancy and from their children at age 2 years. Pre- and postnatal observations limited the response rate and final sample size; data from 147 participants were included in the analysis. Children's health status was assessed at 24 months of age by using a questionnaire administered to the mothers. We studied associations between the urine level of phthalates and the presence of food allergy and atopic dermatitis in logistic regression analysis. All associations were adjusted for independent risk factors of dependent variables. Associations with atopic dermatitis were adjusted for the effect of atopy in the family, the father's education, frequency of house cleaning, and breastfeeding; associations with food allergy were adjusted for the presence of pets at home during pregnancy and breastfeeding. RESULTS: The prevalence of the outcomes were as follows: atopic dermatitis, 12.2%, and food allergy, 48.9%. We showed that higher urine concentrations of monobenzyl phthalate in mothers during pregnancy increased the risk of food allergy in children during the first 2 years of life (odds ratio 4.17 [95% confidence interval, 1.17-17.89]). There were no associations with children's urine and allergic symptoms. CONCLUSIONS: Results of our study indicated awareness of environmental factors that may affect children's health because the phthalates were shown to be risk factors for food allergy in children.

Excretion of urinary histamine and N-tele methylhistamine in patients with gastrointestinal food allergy compared to non-allergic controls during an unrestricted diet and a hypoallergenic diet.

BACKGROUND: Patients with gastrointestinal food allergy are characterised by increased production of mast cell derived mediators upon allergen contact and present often with unspecific symptoms. The aim of this study was to evaluate urinary histamine and methylhistamine excretion in patients with food allergy and to compare their values with food-tolerant controls. METHODS: In a retrospective case control study the urinary excretion parameters were analysed from 56 patients (40.9, 19 - 58 years) in whom later food challenge tests confirmed food allergy. During their diagnostic work-up urine was collected during a 12-h period under an unrestricted diet with staple foods and a hypoallergenic potato-rice-diet (each 2 days). Healthy controls underwent the same diet types to define normal excretion parameters. Urinary histamine and n-methylhistamine were determined by ELISA or tandem mass spectrometry, respectively, and were expressed as median (25 - 75% range, µg/mmol creatinine x m(2)BSA). RESULTS: During unrestricted diet urinary histamine was significantly higher in gastrointestinal food allergy than healthy controls (1.42, 0.9 - 2.7 vs 0.87, 0.4 - 1.3; p < 0.0001), while the difference between both groups became marginal during potato-rice diet (1.30, 0.7 - 2.1 vs 1.05, 0.5 - 1.5; p = 0.02). N-methylhistamine was found to be significantly elevated in gastrointestinal food allergy both during unrestricted diet (7.1, 5.0 - 11.2) and potato-rice diet (5.7, 3.7 - 8.7) compared to controls (p < 0.0001). Interestingly, urinary methylhistamine excretion (p < 0.004) and clinical symptom score (p < 0.02) fell significantly when the diet was switched from unrestricted to hypoallergenic food, but was not correlated with symptom scores. CONCLUSIONS: In gastrointestinal food allergy significantly higher levels of urine histamine and methylhistamine excretion were found under unrestricted diet, reflecting an increased secretion of histamine due to offending foods. Measurement of urinary n-methylhistamine levels may help to find out patients with increased histamine production and/or food-allergen induced clinical symptoms, respectively.

Urinary levels of triclosan and parabens are associated with aeroallergen and food sensitization.

BACKGROUND: Endocrine-disrupting compounds (EDCs) have immune-modulating effects. We were interested in determining their association with allergic sensitization. OBJECTIVE: We sought to determine the association between EDCs and allergic sensitization and whether this relationship depends on the antimicrobial properties of the EDCs, sex, or both. METHODS: Data were obtained from the 2005-2006 National Health and Nutrition Examination Survey in which urinary bisphenol A; triclosan; benzophenone-3; propyl, methyl, butyl, and ethyl parabens; and specific IgE levels were available for 860 children. Aeroallergen and food sensitizations were defined as having at least 1 positive (≥ 0.35 kU/L) specific IgE level to an aeroallergen or a food. Logistic regression was used to determine the association of EDCs and sensitization. Analyses were adjusted for urinary creatinine level, age, sex, ethnicity, and poverty index ratio. RESULTS: The odds of aeroallergen sensitization significantly increased with the level of the antimicrobial EDCs triclosan and propyl and butyl parabens (P ≤ .04). The odds of food sensitization significantly increased with the level of urinary triclosan among male subjects (odds ratio for third vs first tertiles, 3.9; P= .02 for trend). There was a significant interaction between sex and triclosan level, with male subjects being more likely to be food sensitized with exposure (P= .03). Similar associations were not identified for the nonantimicrobial EDCs bisphenol A and benzophenone-3 (P > .2). CONCLUSIONS: As a group, EDCs are not associated with allergen sensitization. However, levels of the antimicrobial EDCs triclosan and parabens were significantly associated with allergic sensitization. The potential role of antimicrobial EDCs in allergic disease warrants further study because they are commonly used in Western society.

Helicobacter pylori as a protective factor against food allergy.

BACKGROUND: There is some evidence that Helicobacter pylori (Hp) infection may protect against asthma and allergy. The aim of the present study was to analyse the prevalence of Hp infection in adults with proven food allergy and to compare it with that in appropriate healthy controls. In addition, the effects of infection with Hp on urinary excretion of N-tele-methylhistamine and production of IgE and allergy mediators such as eosinophilic cationic protein (ECP) and mast cell tryptase, were assessed. MATERIAL/METHODS: Hp infection, the production of IgE and several allergy mediators and mucosal expression of interleukin-4 were measured in 42 patients with food allergy and compared with those in 20 healthy subjects. RESULTS: The prevalence of Hp infection among adult food allergy patients was 33.3% and it was significantly lower than that in the control group (40%). The excretion of urinary N-tele-methylhistamine was higher in food allergy patients than in healthy controls. In food allergy patients with Hp infection, the serum ECP was significantly lower than in food allergy patients without Hp infection. The serum IgE level was significantly higher in food allergy patients infected with Hp than in food allergy patients without Hp infection. CONCLUSIONS: We conclude that: 1) Hp infection is associated with a decreased risk for food allergy; 2) presence of Hp in food allergy patients has ameliorating effect on the production of allergy mediators such as ECP and mast cell tryptase and 3) Hp infection appears to be a protective factor against food allergy.

Measurements of eosinophil activation before and after food challenges in adults with food hypersensitivity.

BACKGROUND: Objective assessment of inflammatory reactions in the gastrointestinal tract could be useful in the diagnosis of food hypersensitivity. The aim of the present study was to investigate the involvement of eosinophils and mast cells in the inflammatory response of patients with food hypersensitivity before and after food challenges. METHODS: Eleven patients (4 with IgE-mediated allergy and 7 without) with food hypersensitivity and positive double-blind, placebo-controlled food challenge were subjected to food challenge in a single-blinded fashion. Four subjects with no known food hypersensitivity were recruited as controls. Placebo was given after a 1-week washout period followed by an active dose. Stool, urinary and serum samples were collected and symptoms were recorded in a diary. Fecal samples were analyzed for eosinophil protein X (F-EPX) and tryptase; urinary samples for EPX (U-EPX) and leukotriene E4 (U-LTE4) and serum samples were analyzed for eotaxin and food-specific IgE antibodies. RESULTS: Patients with IgE-mediated food allergy had increased levels of F-EPX compared to controls and tended to have lower serum levels of eotaxin compared to non-allergic patients and controls. U-LTE4 was significantly higher in allergic patients compared to non-allergic patients after challenge. Moreover, F-EPX correlated to U-LTE4 (p = 0.011). Reported symptoms, abdominal pain, distension, flatulence and nausea were similar in the allergic and non-allergic patients. CONCLUSION: The results strongly indicate that eosinophils are activated in the gastrointestinal tract of food-allergic patients but not in patients with non-allergic food hypersensitivity. Due to the inconsistent pattern of symptoms after placebo and active food challenge, it was not possible to relate the levels of inflammation markers to the recorded symptoms.

Serum tryptase and urinary 1-methylhistamine as parameters for monitoring oral food challenges in children.

To study the usefulness of urinary 1-methylhistamine and serum tryptase concentration as monitoring parameters in clinical settings, we investigated 32 children with atopic dermatitis and suspected food allergy during oral food challenges with eggs and cow's milk. Urinary 1-methylhistamine (MH) excretion increased significantly within 1 h after positive oral food challenges (p < 0.006), but showed considerable variation in negative challenges. MH seems to be a sensitive parameter (92.8%), but its specificity is insufficient (37.7%). In the group of 16 positive oral food challenges serum tryptase concentration increased significantly (p < 0.02) directly after provocation and remained elevated up to 2 h after provocation. No variation was observed in negative challenges or nonatopic controls. Serum tryptase concentration seems to be specific for marked clinical reactions after oral food challenges (100%), but its sensitivity was low (25%) and not superior to evaluation by clinical means. We conclude that, despite positive results for the group of children, MH and serum tryptase concentrations are not useful parameters for monitoring oral food challenges in an individual child due to insufficient sensitivity and specificity.

Increased urinary excretion of angiotensin during anaphylactoid reactions.

Immunoreactive angiotensin I (ANG I) and angiotensin II (ANG II) were measured in human urine, after purification on octadecasilyl-silica cartridges. The total daily excretion of ANG I and II in healthy volunteers was 292.2 +/- 62.5 and 12.2 +/- 2.5 pmol/24 h (mean +/- SEM; n = 14). No differences in the concentrations of ANG I or II were detected between females and males. Although lower levels of ANG I and II were found during the nighttime, no clear-cut circadian rhythm in the excretion of the peptides was found. ANG II was not degraded in acidified urine which shows the effective inhibition of ANG-II-degrading enzymes. Oral provocation tests (OPT) in patients with a history of anaphylactoid reactions (AR) to drugs, foods and food additives were associated with elevated ANG I and II concentrations when symptoms of anaphylaxis occurred. The excretion of ANG I increased by a factor of 7.8 +/- 2.4 and the excretion of ANG II by a factor of 6.1 +/- 1.6 (mean +/- SEM; n = 15). In patients with negative OPT and no clinical symptoms of anaphylaxis, the levels of ANG I and II remained unchanged (n = 26). It is concluded that angiotensin peptides play a role during the events of AR. The peptides may be considered as counteracting factors which stabilize cardiovascular functions.

[Dynamic diagnosis of allergy by the sequential measurement of mediators: apropos of a case of food allergy]. / Du diagnostic dynamique de l'allergie par le dosage séquentiel des médiateurs: à propos d'une observation d'allergie alimentaire.

Objective improvement in the diagnosis of immuno-allergology can only be obtained by application of reliable and reproducible immuno-biological methods, but until now, only measurements of total and specific IgE can be used and this has certain limitations. Presence of specific serum IgE, correlated with skin tests, favours a sensitization and implies nothing about the responsibility of the allergens. This is why we must consider if a definite improvement of diagnostic methods can be obtained by measurement of mediators. From an observation of food allergy to pork meat, we now show that it is possible to use sequential measurements of the mediators plasma histamine and urinary methylhistamine, ECP and serum tryptase to refine the diagnosis and provide proof of the responsibility of the food allergen. We report here a didactic observation which is characterised by reproducibility and specificity of the measurements. It illustrates the progress in diagnostic methods in allergy: we give a statistical diagnosis by measurement of antibodies and a dynamic diagnosis by measurement of mediators.

Poor sulphoxidation ability in patients with food sensitivity.

Patients with well defined reactions to foods were examined for their ability to carry out both sulphur and carbon oxidation reactions by using carbocisteine and debrisoquine as probe compounds. The proportion of poor sulphoxidisers (58 of 74) was significantly greater than that of a previously determined normal control population (67 of 200; p less than 0.005). The proportion of poor carbon oxidisers was not significantly different from the controls. Metabolic defects may play a part in the pathogenesis of adverse reactions to foods.