Health-related quality of life in children with objectively diagnosed staple food allergy assessed with a disease-specific questionnaire.

AIM: Among Swedish children of 0-12 years old, we investigated various food allergy-related exposures associated with health-related quality of life using a food allergy-specific questionnaire among children allergic to the staple foods cow's milk, hen's egg and/or wheat, and contextualised worse food allergy-associated health-related quality of life using a generic questionnaire versus controls. METHODS: In total, 85 children with objectively diagnosed allergy to the staple foods were included as cases, and 94 children matched for age and sex were included as controls. We administered a food allergy-specific parent-completed questionnaire originally developed by EuroPrevall to cases only, and a generic health-related quality of life questionnaire (EuroQol Health Questionnaire, 5 Dimensions; EQ 5-D); to both cases and controls. RESULTS: Hen's egg was the most common offending staple food, affecting 76% of cases. Approximately 7% of cases were allergic to all three staple foods. Parent-reported respiratory and cardiovascular symptoms were associated with worse health-related quality of life. Elements of disease severity [previous anaphylaxis (p < 0.001); epinephrine autoinjector prescription (p < 0.003)] were negatively associated with health-related quality of life. Cases had worse health-related quality of life measured by the EQ-5D compared to controls (p < 0.01). CONCLUSION: The use of a disease-specific questionnaire revealed that disease severity in children with objectively diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat is associated with worse health-related quality of life. The use of a generic questionnaire confirmed that cases have worse health-related quality of life than controls.

Socioeconomic evaluation of well-characterized allergy to staple foods in adults.

BACKGROUND: The aim of the present study was to evaluate if total, direct, indirect, and intangible costs differ between a cohort of adults with well-characterized allergy to staple foods ('cases') and controls. METHODS: Swedish adults with objectively diagnosed food allergy to cow's milk, hen's egg, and/or wheat were recruited at an outpatient allergy clinic. Controls age- and sex-matched to cases were recruited from the same geographic area. For assessing the household costs of food allergy, a disease-specific socioeconomic questionnaire, developed within EuroPrevall, was utilized. RESULTS: Overall annual total costs at the household level were significantly higher among adults with food allergy compared with controls (the difference amounted to 8164 €), whereas direct costs did not differ between cases and controls. However, household healthcare costs and costs for medicines were significantly higher for cases vs controls. Furthermore, indirect costs were significantly higher for households with food-allergic adults vs households without food-allergic adults. Specifically, more time was spent on performing domestic tasks due to a family member's food-allergy-related illness, as well as shopping and preparing food, and seeking food-allergy-related information. Presence of food allergy also affected intangible costs. Adults with food allergy experienced overall lower health status compared with controls. CONCLUSIONS: Swedish adults with allergy to staple foods have higher total costs determined as direct, indirect, and intangible costs using the disease-specific socioeconomic questionnaire. Thus, total costs were 8164 € higher per year in households with at least one adult allergic to staple foods compared with controls.

Th2-associated immunity to bacteria in teenagers and susceptibility to asthma.

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility. We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes. IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk. The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterial-induced inflammation.

Reported symptoms to peanut between 4 and 8 years among children sensitized to peanut and birch pollen - results from the BAMSE birth cohort.

BACKGROUND: Specific IgE tests are sometimes difficult to interpret due to structural similarities between certain food and pollen allergens. This may be the reason why concomitant sensitization to peanut and birch pollen is frequently seen. The aim of this study was to investigate reported symptoms to peanut- and birch pollen in relation to sensitization. METHODS: The data originate from 1928 children in the BAMSE birth cohort. Background factors and clinical parameters were obtained and the levels of IgE antibodies to peanut and birch pollen measured at 4 and 8 years. RESULTS: IgE antibodies to peanut were found in 5.5% and 7.4% of the children at 4 and 8 years, respectively. The IgE antibody levels to peanut were higher in children sensitized to peanut but not birch than in children sensitized to peanut and birch among both 4- and 8-year-olds (P = 0.093 and P = 0.003, respectively). Eight-year-olds sensitized to peanut but not birch, more often reported symptoms to peanut than children sensitized to both peanut and birch pollen (76%vs 46%, P = 0.002). The probability of reported symptoms to peanut increased significantly with increasing IgE levels to peanut, especially in 8-year-olds not sensitized to birch. CONCLUSIONS: Children sensitized to both peanut and birch pollen are less likely to report symptoms to peanut than children sensitized to peanut but not to birch pollen at 8 years. This is likely due to cross reactions between birch pollen and peanut and can explain the high sensitization rate to peanut in areas where birch trees are common.

IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds.

BACKGROUND: Allergen-specific IgE testing is often performed with crude peanut extract, but the results may be difficult to interpret because of cross-reactions between peanut and other plant allergens. The aim was to investigate IgE reactivity to peanut allergen components in children from a birch-rich region in relation to pollen sensitization and peanut symptoms. METHODS: From a birth cohort, clinical parameters were obtained through questionnaires and IgE antibody levels to peanut and birch pollen were measured. Different peanut/birch sensitization phenotypes were defined among 200 selected children. IgE reactivity to peanut and pollen allergen components was analysed using microarray technique. RESULTS: Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the peanut allergens Ara h 1, 2 or 3 but not to Ara h 8 (n = 46) vs 17% of children with IgE reactivity to Ara h 8 but not to Ara h 1, 2 or 3 (n = 23), P < 0.001. Furthermore, symptoms were more severe in children with Ara h 1, 2 or 3 reactivity. Children with IgE reactivity both to Ara h 2 and to Ara h 1 or 3 more often reported peanut symptoms than children with IgE only to Ara h 2 (97%vs 70%, P = 0.016), particularly respiratory symptoms (50%vs 9%, P = 0.002). CONCLUSIONS: IgE analysis to peanut allergen components may be used to distinguish between peanut-sensitized individuals at risk of severe symptoms and those likely to have milder or no symptoms to peanut if sensitized to pollen allergens and their peanut homologue allergens.

Asthma prediction in school children; the value of combined IgE-antibodies and obstructive airways disease severity score.

BACKGROUND: Allergic sensitisation increases the risk for asthma development. In this prospective birth cohort (Environment and Childhood Asthma) study, we hypothesized that combining quantitative measures of IgE antibodies (Sigma-IgE) and Severity score of obstructive airways disease (OAD) at 2 years of age (Severity score) is superior to predict current asthma (CA) at 10 years than either measure alone. Secondarily, we assessed if gender modified the prediction of CA. METHODS: A follow-up study at 10 years of age was performed in 371 2-year-old children with recurrent (n = 219) or no (n = 152) bronchial obstruction with available serum analysed for Sigma-IgE to common food and inhalant allergens through a panel test, Phadiatop Infant) (Phadia, Uppsala, Sweden). Clinical variables included allergic sensitisation and exercise testing to characterise children with CA vs not CA at 10 years and the Severity score (0-12, 0 indicating no OAD) was used to assess risk modification. RESULTS: Severity score alone explained 24% (Nagelkerke R(2) = 0.24) of the variation in CA, whereas Sigma-IgE explained only 6% (R(2) = 0.06). Combining the two increased the explanatory capacity to R(2) = 0.30. Gender interacted significantly with Sigma-IgE; whereas Severity score predicted CA in both genders, the predictive capacity of Sigma-IgE for CA at 10 years was significant in boys only. CONCLUSION: Combining Sigma-IgE to inhalant allergens and Severity score at 2 years was superior to predict asthma at 10 years than either alone. Severity score predicted CA in both genders, whereas Sigma-IgE significantly predicted CA in boys only.

Patterns of quantitative food-specific IgE-antibodies and reported food hypersensitivity in 4-year-old children.

BACKGROUND: Diagnosis of food hypersensitivity (FHS) is difficult and interpretation of food allergy tests is complicated. OBJECTIVE: To investigate the probability of reported FHS in relation to levels of food-specific IgE-antibodies (AB) in a population-based setting of 4-year-old children (n = 2336). METHODS: Information on FHS was obtained from a questionnaire and specific IgE-AB to milk, egg, fish, peanut, soy and wheat were analysed. RESULTS: Thirty-one per cent of the children with reported FHS (n = 284) were sensitized (> or =0.35 kU(A)/l) to at least one of the tested foods compared with 11% of children without FHS (n = 2052). Furthermore, the probability of reported symptoms to milk, egg and fish increased with increasing levels of food-specific IgE-AB to the same food allergens. A similar trend was seen for peanut and wheat, but not for soy. Increasing levels of specific IgE-AB to milk or egg were also associated with an increasing risk of reported symptoms caused by other foods. CONCLUSIONS: Quantitative measurements of IgE-AB to milk, egg and fish are useful to evaluate IgE-associated FHS in preschool children also in a population based sample. Such measurements appear to be of limited value for soy bean and wheat, in particular as a screening method.

Primary care: the cornerstone of diagnosis of allergic rhinitis.

Allergic rhinitis (AR) is a very common disease with over 600 million people (200 million of them with concomitant asthma) worldwide suffering from it. The majority of patients who seek medical advice are seen in primary care. Although there is a selection of guidelines focused on the management of AR, there is a paucity of guidance on how best to identify patients who would most benefit from treatment. The aim of this paper was to review the best practice for primary care with respect to the diagnosis of AR within that clinical environment.

Detection of local mast-cell activity in patients with food hypersensitivity.

BACKGROUND: Mast cells play a central role in many inflammatory diseases and assessment of their activation may be of use to provide objective confirmation of the outcome of food challenge in the diagnosis of food hypersensitivity. However, to date, assessment of mast-cell activation using serum markers has been unsuccessful. OBJECTIVE: The aim of this study was to explore whether locally released tryptase could be detected in stool samples from patients with food hypersensitivity. METHODS: Nine patients (median age, 55 years; range, 26 - 68 years) with food hypersensitivity confirmed by double-blind placebo-controlled food challenge were included in the study. Tryptase concentration was assessed in stool samples collected before and after an open food challenge at home and symptoms were recorded throughout the study. Tryptase concentration was also assessed in stool samples from 16 apparently healthy individuals (median age, 44 years; range, 27 - 72 years). RESULTS: Measurement of fecal tryptase levels in 16 healthy control subjects revealed an upper limit of the normal range (mean + 2 SD of log transformed data) of 10 ng/g. Fecal tryptase levels exceeded 10 ng/g in 7 out of 9 patients in one or more samples obtained during the study. The tryptase levels varied between patients in response to the food challenge and the individual mean levels of tryptase correlated with the corresponding levels of the inflammatory marker eosinophil protein X (rho = 0.7500, P = .02). CONCLUSION: Measurement of tryptase levels in stool samples is feasible using the method described here. Our results revealed elevated concentrations of fecal tryptase in patients with food hypersensitivity. However, several factors, including food exposure, may account for the increase in fecal tryptase and further studies are necessary to elucidate the role of mast cells in food hypersensitivity.

A fluorescence method for the visualization of inflammatory cells in intestinal mucosa.

Treatment of paraffin or cryostat sections from rat, rabbit and man, with fluorescein isothiocyanate (FITC) in buffer (1 microgram/l), resulted in visualization of highly fluorescent leukocytes with a granular staining in light microscopy. FITC staining of paraffin-embedded colonic tissue was compared with three other staining methods, i.e., (1) FITC-conjugated anti-neutrophil antibodies, (2) endogenous peroxidase with 3,3-diaminobenzidine, and (3) FITC-conjugated Lotus tetragonolobus lectin. Good correlations between FITC staining and the three other methods were found (r:0.97, 0.98 and 0.98; P less than 0.001). Inhibition of receptors for the FITC conjugates prior staining, by preincubation with unconjugated anti-neutrophil antibodies or L-fucose, abolished the staining with antibodies and lectin. This study shows that staining with unlabeled FITC represents a quick and convenient method for the estimation of phagocytic cells (polymorphonuclear cells and macrophages) in histological specimens.

Protective factors in milk and the development of the immune system.

The neonate is immature in certain immunologic functions. The slow development of secretory immunoglobin A (IgA) seems to be compensated by selective transfer of secretory IgM into exocrine secretions on mucous membranes during the first few months of life. Secretory IgA and secretory IgM antibodies against Escherichia coli and poliovirus are already found in the neonate, possibly in response to the maternal anti-idiotypic IgG antibodies transplacentally exposing the fetus. Via such a mechanism, food antibodies could occur before direct food exposure in the infant. Human milk provides large amounts of antibodies (as a crude comparison, about 50 times the amount of antibodies given to a patient with hypogammaglobulinemia). The milk antibodies, dominated by secretory IgA, protect especially against intestinal infections. The milk also contains oligosaccharide analogues to epithelial receptors for bacteria. They, as well as a number of milk components such as lactoferrin and lysozyme, may contribute to host defense. The food antibodies in human milk may influence the infant's immune response to foreign food proteins introduced during weaning.

Immune complex induced experimental colitis: beneficial effect of sulphasalazine in rabbits.

Experimental colitis was induced in rabbits by exposing the colon mucosa to 1% formalin followed by i.v. injections of soluble immune complexes made with antigen in excess. The animals were preimmunized with Escherichia coli O14:K7:H--inducing antibodies cross-reactive to intestinal epithelium. Animals with this colitis were divided in two groups. One group was treated with sulphasalazine and the other was given vehicle only. Sulphasalazine was administered daily at 125.5 mumol (50 mg) per kg body weight. The administration was started at the same day as the colitis was initiated. At Day 6, 13 and 30 following induction of colitis, biopsies were sampled and histologically evaluated. Inflammation was assessed by scores for inflammatory cells, crypt distortion, decreased crypt number and presence of crypt abscesses, thus corresponding to the picture seen in humans. A statistically significant lower score of inflammation was seen on Day 6 and 13 (P less than 0.01) and on Day 30 (P less than 0.05) following induction of colitis in animals treated with sulphasalazine.

Mucosal immunity.

Mucosal defense is provided by a number of host factors countering the specific virulence factors of the many microorganisms infecting the mucous membranes. Secretory IgA antibodies presumably play an important role. Increase of the sIgA antibodies may most advantageously be attained by parenteral immunization, following mucosal priming. This was demonstrated in a rat model, where it was also noted that antigen injection into PP induced high milk IgA antibody levels. In man, parenteral vaccination against polio increased the sIgA antibody levels in the milk of mothers previously exposed naturally to the poliovirus. The response was relatively short-lived. In the previously unexposed, there was little or no response. By contrast peroral immunization with live poliovirus vaccine did not increase, or even decrease, the milk sIgA poliovirus antibody levels. Although salivary sIgA antibodies against antigens of colonizing E. coli appear during the first days of life, they are slow to increase. This deficiency is richly compensated for by all the sIgA antibodies that are provided the baby through the milk. No transfer of dimeric IgA into the milk could be shown in lactating rats, in contrast to what has been reported in mice. There is no evidence for a contribution to milk sIgA from serum in man. Close to parturition, human milk often contains some 7S IgA and various sizes of free SC, in addition to the dominating 11S sIgA. A few days later there is almost exclusively monomeric SC and 11S sIgA. IgG antibodies also play a role at the mucosal level. IgG2 antibodies against the bacterial polysaccharide capsule are as slow to appear as sIgA in ontogeny, possibly explaining the prevalence of infections with encapsulated bacteria and the poor response to polysaccharide vaccines in early childhood. Other defense factors preventing infections by way of mucous membranes may be important. Thus, oligosaccharides present in human milk seem to specifically prevent pneumococcal attachment to retropharyngeal cells. This anti-attachment capacity, in addition to that provided by milk and salivary IgA antibodies, may explain why breast-fed babies have less otitis media than formula-fed ones.

The inflammatory marker serum eosinophil cationic protein (ECP) compared with PEF as a tool to decide inhaled corticosteroid dose in asthmatic patients.

The objective of this study was to compare the inflammatory marker eosinophil cationic protein (ECP) with peak expiratory flow (PEF) in determining the therapeutic needs of inhaled corticosteroids in asthma patients assessed as asthma symptoms. A randomized, single-blind study over 6 months was performed at six specialist centres in Europe. In total, 164 adult patients with moderate to severe symptomatic asthma and regular use of inhaled corticosteroids were included. After a run-in period of 2 weeks patients were randomly allocated to the ECP or the PEF monitoring group. The dose of inhaled cort costeroids was adjusted every fourth week based on the current serum ECP value or pre-bronchodilator morning PEF values as surrogate markers of therapeutic needs. At the end of the study there were no statistically significant differences in the mean daily symptom score or the percentage of symptom-free days between the two groups. The mean daily dose of inhaled corticosteroids was similar in the two groups at the start of the study but the algorithms used to adjust the dose of inhaled corticosteroids resulted in an increased use of inhaled corticosteroids in both groups. The mean daily dose of inhaled corticosteroids over the whole study period was significantly lower in the ECP group compared withthe PEF group (1246 vs. 1667 microg, P = 0.026). In the ECP group, forced expiratory volume in I sec (FEV)% predicted was lower at the end ofthe study compared with the begining (92% vs. 87%, P = 0 .0009), although there was no significant difference between the two groups. None of the used algorithms for ECP and PEF led to improvement in symptom scores, in spite of increased doses of inhaled corticosteroids. In this respect, both methods were equivalent and insufficient. Recommendations suggesting lung function tests in current guidelines may be difficult to translate into clinical practice, however, a combination of inflammatory markers, lung function and symptoms may still improve asthma control.

Secretory IgA antibodies to enterobacterial virulence antigens: their induction and possible relevance.

1) Milk and salivary s-IgA antibodies are via the homing of IgA producing cells from the Peyer's patches closely connected with antigenic stimuli in the intestine. This explains the presence in human milk of s-IgA antibodies against E. coli O and K antigens, V. cholerae and Shigella O antigens, E. coli and V. cholerae enterotoxins. These secretory antibodies can be induced by intestinal exposure and boosted by parenteral vaccination. 2) Preliminary data suggest that the IgA response in the urinary tract and possibly in the lung may be involved in the homing mechanism as well. 3) The protective role of the milk s-IgA antibodies to enterobacterial virulence antigens is strongly suggested, as is the protection mediated by urinary antibodies against urinary tract infections.

Update in allergy testing in childhood asthma: how do you know whether you are successfully controlling the patient's inflammation?

The levels of serum eosinophil cationic protein (ECP) in asthmatic patients have been shown to be increased in acute and undertreated asthma as a result of inflammation. ECP is released during in vitro clotting of peripheral blood. The exposure of the atopic individual to an offending allergen stimulates the activation of the blood eosinophils and their release of ECP into serum. Serum ECP levels reflect avoidance of the allergen, and successful treatment of asthma inflammation with corticosteroids cause a reduction of the inflammation in the lung. When individual patients with asthma are followed, the level of serum ECP can be used (1) as an early indicator of the degree of inflammation, (2) for monitoring the efficacy of corticosteroid therapy, and (3) for possible noncompliance with treatment.

Has the increase in the prevalence of asthma and respiratory symptoms reached a plateau in Stockholm, Sweden?

SETTING: An increase in the prevalence of asthma has previously been reported worldwide. However, the current trend is debatable. OBJECTIVE: To assess changes in the prevalence of asthma and respiratory symptoms in a defined study area in Stockholm, Sweden, using identical methods. DESIGN: A questionnaire was sent by mail in 1996 and 2007 to randomly selected subjects aged 20-69 years. On both occasions, 8000 subjects received the questionnaire, with response rates of 72% and 68%, respectively. Questions on asthma, respiratory symptoms, asthma medication and possible determinants were included. Logistic regression analysis was used to assess determinants. RESULTS: Ever asthma increased from 8.7% in 1996 to 11.0% in 2007 and physician-diagnosed asthma from 7.6% to 9.3%. The proportion of asthma patients reporting one to two symptoms increased by 14% during the study period. There were few significant changes in the prevalence of respiratory symptoms: wheeze in the previous 12 months (15.9-17.3%), wheezing with breathlessness apart from cold (3.2-4.1%) and recurrent wheeze (8.3-6.8%). There was no major difference in the risk factor pattern between the surveys. CONCLUSION: An increase in the prevalence of asthma with few symptoms as well as an unchanged prevalence of symptoms was demonstrated, which may indicate a change in diagnostic practices.