The Finnish versions of food allergy quality of life questionnaires including parent form 10.

AIM: Examining health-related quality of life (HRQoL) is important to improve patient care. In this study, we translate and evaluate the Finnish versions of the Food Allergy Specific Quality of Life Questionnaires (FAQLQs) from a Finnish perspective and undertake a detailed evaluation of the 10-question Parent Form Questionnaire (FAQLQ-PF10). METHODS: This validation study was performed to evaluate the Finnish versions of the FAQLQs. Validation was performed by analysing clinical characteristics, factor loadings and Cronbach's α reliability estimates. The inclusion criteria for participants in this study were having a doctor-diagnosed food allergy or being a parent of a child with a doctor-diagnosed food allergy and being able to answer the questionnaire in Finnish. RESULTS: Altogether, 247 questionnaires were completed in this study. Most of the respondents had multiple food allergies (77%, 189/247). Spearman's correlations related to the 10-question parent form (FAQLQ-PF10), the 30-question parent form (FAQLQ-PF) and the Food Allergy Severity Measurement-Parent Form (FAIM-PF) were statistically significant (p value = 0.000-0.007). The reliability of the Finnish versions of the FAQLQs measured by Cronbach's α was overall good (0.75-0.981). CONCLUSION: The Finnish versions of the FAQLQs are reliable and suitable to use, and the FAQLQ-PF10 has good usability.

Interaction of mediators and effector cells in cashew nut-induced anaphylaxis.

BACKGROUND: The underlying mechanisms of an immediate food-induced allergic reaction involve mast cell degranulation and recruitment of other effector cells, such as lymphocytes, eosinophils, and basophils. How the interaction of various mediators and cells results in anaphylaxis is not fully understood. OBJECTIVE: To evaluate changes in platelet-activating factor (PAF), platelet-activating factor acetylhydrolase (PAF-AH), tryptase, eosinophils, basophils, and eosinophil cationic protein (ECP) in cashew nut-induced anaphylaxis. METHODS: Open cashew nut challenges were performed on 106 children (aged 1-16 years), sensitized to cashew nut, with earlier allergic reaction to cashew nut or no known exposure. PAF, PAF-AH, tryptase, ECP, eosinophils, and basophils were measured at 4 time points. RESULTS: Of 72 challenges with positive results, 34 were defined as anaphylactic. Eosinophil count decreased progressively during an anaphylactic reaction at all 4 time points (P < .005*) compared with baseline. Although significant PAF elevation was observed 1 hour from moderate-to-severe reaction (P = .04*), PAF seemed to peak especially in anaphylaxis but did not achieve statistical significance. PAF peak ratio (peak PAF/baseline PAF) was significantly greater in anaphylactic reactions compared with the no-anaphylaxis group (P = .008*). Maximal percentage change in eosinophils revealed negative correlation to severity score and PAF peak ratio (Spearman's rho -0.424 and -0.516, respectively). Basophils decreased significantly in moderate-to-severe reactions and in anaphylaxis (P < .05*) compared with baseline. Delta-tryptase (peak tryptase minus baseline) did not differ significantly between anaphylaxis and the no-anaphylaxis subgroups (P = .05). CONCLUSION: PAF is a specific anaphylaxis biomarker. Marked decline of eosinophils during anaphylaxis may be related to robust secretion of PAF reflecting migration of eosinophils to target tissues.

Molecular allergy diagnostics in predicting oral cow's milk challenge outcome in Finnish children.

Background: Oral food challenges (OFC) are required to diagnose food allergies but are resource-intensive. Objective: To reduce the need for OFCs, we sought to determine serum specific immunoglobulin E (sIgE) cutoff levels for cow's milk and its major allergens predicting oral milk challenge outcomes in children with suspected cow's milk allergy. Methods: A total of 135 Finnish children (median age, 1.8 years [range, 1.0-14.1 years]) with suspected cow's milk allergy underwent open OFC with unheated cow's milk. The sIgE levels to milk (f2), casein (Bos d 8), alpha-lactalbumin (Bos d 4), beta-lactoglobulin (Bos d 5), and bovine serum albumin (BSA) (Bos d 6) were measured and compared with the challenge outcomes. Results: Of the 135 OFCs, 5 were excluded from the study due to purely subjective symptoms. Of the 130 remaining OFCs, 98 results (75%) were positive. In a receiver operating characteristic analysis with 1-2-year-old children, no individual allergen sIgE had a better area under the curve than milk sIgE (0.824). A milk sIgE level > 6.30 kU/L gave 94% specificity and 33% sensitivity for positive OFCs. In 3-14-year-old children, a cutoff value >13.9 kU/L predicted a positive OFC result with 93% specificity and 25% sensitivity. Children with moderate-to-severe reactions had higher sIgE levels to milk, alpha-lactalbumin, and BSA than did children with mild reactions. Conclusion: Molecular allergy diagnostics did not improve the predictive performance compared with milk sIgE. The milk sIgE value that exceeds the cutoff for 95% specificity in combination with the clinical history may help to reduce the need for OFCs. The severity of an allergic reaction cannot reliably be predicted from sIgE measurements.

Bronchial hyperresponsiveness and asthma during oral immunotherapy for egg or peanut allergy in children.

Background: Bronchial hyperresponsiveness (BHR) and asthma are frequently present in children with food allergy. We assessed BHR in children receiving oral immunotherapy (OIT) for persistent egg or peanut allergy and examined whether OIT affects asthma control. Methods: Methacholine challenge testing was performed in 89 children with persistent egg or peanut allergy diagnosed by double-blind, placebo-controlled food challenge and 80 control children without food allergy. Of the 89 food-allergic children, 50 started OIT for egg allergy and 39 for peanut allergy. Sensitization to aeroallergens was evaluated by skin prick testing. Forty of the 89 children with regular controller treatment for asthma underwent methacholine challenge testing and 34 measurement of exhaled nitric oxide (FeNO) at baseline and after 6-12 months of OIT. Results: Methacholine challenge testing revealed significant BHR in 29/50 children (58%) with egg allergy, 15/39 children (38%) with peanut allergy, and 6/80 controls (7.5%). The mean cumulative dose of methacholine causing a 20% fall in FEV1 differed significantly between the egg and peanut-allergic versus the control children (1009 µg, 1104 µg, and 2068 µg, respectively, p < 0.001). Egg or peanut OIT did not affect lung function, the degree of BHR or FeNO levels in children with asthma and had no adverse effect on asthma control. Lung function or BHR did not associate with the OIT outcome. Conclusion: BHR was significantly more frequent in children with persistent egg or peanut allergy than in children without food allergy. Oral immunotherapy did not increase BHR and was safe for children on regular asthma medication.

Optimizing tools for evaluating challenge outcomes in children with cashew nut allergy.

BACKGROUND: The incidence of cashew nut anaphylaxis is increasing and there is a need for accurate diagnostic tests. Age-specific cutoffs in children are lacking. Changes in serum tryptase levels are not well documented in pediatric food allergy, except in anaphylaxis. OBJECTIVE: To evaluate the ability of various tests to diagnose cashew nut allergy and to predict reaction severity. We also investigated changes in tryptase and their correlation to reaction severity. METHODS: We performed an open cashew nut challenge on 106 children (aged 1-16 years), who were sensitized to cashew nut with either previous allergic reaction to cashew nut or no known exposure. We analyzed the accuracy of Ana o 3 immunoglobulin E (IgE), cashew nut IgE, skin prick test, basophil activation test (BAT), and combinations thereof to diagnose cashew nut allergy and to predict reaction severity. Tryptase level was measured at the baseline and during an allergic reaction. RESULTS: A total of 72 children had positive challenge outcomes. Ana o 3 IgE seemed to be the best single test to diagnose cashew allergy, with a 0.97 kU/L cutoff exhibiting 94.1% specificity and 61.1% sensitivity. Though BAT values of at least 22.8% best predicted reaction severity, with 91.7% specificity and 60.7% sensitivity, the cutoffs were age-specific. Tryptase levels increased substantially 1 to 2 hours after the first allergic symptoms compared with baseline. CONCLUSION: Ana o 3 IgE seems to be the best diagnostic test in pediatric cashew nut allergy, and test combinations do not seem to improve the diagnostics. Cutoffs are age-specific. BAT is promising in predicting reaction severity. Tryptase levels should be measured 1 to 2 hours after initiation of an allergic reaction.

Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants.

BACKGROUND: Infants born by caesarean section or receiving antibiotics are at increased risk of developing metabolic, inflammatory and immunological diseases, potentially due to disruption of normal gut microbiota at a critical developmental time window. We investigated whether probiotic supplementation could ameliorate the effects of antibiotic use or caesarean birth on infant microbiota in a double blind, placebo-controlled randomized clinical trial. Mothers were given a multispecies probiotic, consisting of Bifidobacterium breve Bb99 (Bp99 2 × 108 cfu) Propionibacterium freundenreichii subsp. shermanii JS (2 × 109cfu), Lactobacillus rhamnosus Lc705 (5 × 109 cfu) and Lactobacillus rhamnosus GG (5 × 109 cfu) (N = 168 breastfed and 31 formula-fed), or placebo supplement (N = 201 breastfed and 22 formula-fed) during pregnancy, and the infants were given the same supplement. Faecal samples of the infants were collected at 3 months and analyzed using taxonomic, metagenomic and metaproteomic approaches. RESULTS: The probiotic supplement had a strong overall impact on the microbiota composition, but the effect depended on the infant's diet. Only breastfed infants showed the expected increase in bifidobacteria and reduction in Proteobacteria and Clostridia. In the placebo group, both birth mode and antibiotic use were significantly associated with altered microbiota composition and function, particularly reduced Bifidobacterium abundance. In the probiotic group, the effects of antibiotics and birth mode were either completely eliminated or reduced. CONCLUSIONS: The results indicate that it is possible to correct undesired changes in microbiota composition and function caused by antibiotic treatments or caesarean birth by supplementing infants with a probiotic mixture together with at least partial breastfeeding. TRIAL REGISTRATION: clinicaltrials.gov NCT00298337 . Registered March 2, 2006.

Fucosylated oligosaccharides in mother's milk alleviate the effects of caesarean birth on infant gut microbiota.

One of the most abundant components in human milk is formed by oligosaccharides, which are poorly digested by the infant. The oligosaccharide composition of breast milk varies between mothers, and is dependent on maternal secretor (FUT2) genotype. Secretor mothers produce milk containing α1-2 fucosylated human milk oligosaccharides, which are absent in the milk of non-secretor mothers. Several strains of bacteria in the infant gut have the capacity to utilise human milk oligosaccharides (HMOs). Here we investigate the differences in infant gut microbiota composition between secretor (N = 76) and non-secretor (N = 15) mothers, taking into account birth mode. In the vaginally born infants, maternal secretor status was not associated with microbiota composition. In the caesarean-born, however, many of the caesarean-associated microbiota patterns were more pronounced among the infants of non-secretor mothers compared to those of secretor mothers. Particularly bifidobacteria were strongly depleted and enterococci increased among the caesarean-born infants of non-secretor mothers. Furthermore, Akkermansia was increased in the section-born infants of secretor mothers, supporting the suggestion that this organism may degrade HMOs. The results indicate that maternal secretor status may be particularly influential in infants with compromised microbiota development, and that these infants could benefit from corrective supplementation.

The effect of oral immunotherapy treatment in severe IgE mediated milk, peanut, and egg allergy in adults.

INTRODUCTION: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. OBJECTIVE: We aimed to study if OIT is possible in adults. METHODS: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT. The allergy was confirmed with allergen specific IgE tests and oral food challenges (open in milk allergy and double-blind in peanut and egg allergy). The OIT was performed as open. RESULTS: The median dose of protein that led to discontinuation of allergen challenge because of symptoms was 7.5 mg in milk allergy, 25 mg in peanut allergy, and 15 mg in egg allergy. The median period of OIT was 515 days. Currently on OIT are 6/10 milk allergic patients, 4/9 peanut allergic patients and 3/4 egg allergic patients. The median dose of milk protein increased by 60-fold during OIT compared to the allergen challenge dose. In peanut OIT the median dose increased by eightfold and in egg allergy the dose increased with OIT by 35-fold. Local itching was the most common side effect of OIT (73.9% of the patients), four patients reported having used epinephrine autoinjector and three patients having needed emergency room treatment. CONCLUSIONS AND CLINICAL RELEVANCE: OIT can be given in adult patients with severe milk, peanut, or egg allergy only in selected cases. OIT leads into desensitization but it is not clear whether persistent tolerance can be achieved. Mild adverse events during OIT are common.

High intestinal IgA associates with reduced risk of IgE-associated allergic diseases.

Development of oral tolerance and its stimulation by probiotics are still incomprehensible. Microbial stimulation of the gut may induce a subtle inflammation and induce secretion of mucosal IgA, which participates in antigen elimination. In a cohort of allergy-prone infants receiving probiotics and prebiotics or placebo we studied intestinal IgA and inflammation in the development of eczema, food allergy, asthma, and rhinitis (allergic diseases). We performed a nested unmatched case-control study of 237 infants participating in a randomized double-blind placebo-controlled allergy-prevention trial using a combination of four probiotic strains pre-natally and during 6 months form birth. We measured faecal IgA, alpha1-antitrypsin (alpha1-AT), tumour necrosis factor-alpha (TNF-alpha), and calprotectin at the age of 3 and 6 months. By age 2 yr, 124 infants had developed allergic disease or IgE-sensitization (cases) and 113 had not (controls). In infants with high faecal IgA concentration at the age of 6 months, the risk of having any allergic disease before the age of 2 yr tended to reduce [odds ratio (OR: 0.52)] and the risk for any IgE-associated (atopic) disease reduced significantly (OR: 0.49). High faecal calprotectin at the age of 6 months associated also with lower risk for IgE-associated diseases up to age 2 yr (OR: 0.49). All faecal inflammation markers (alpha1-AT, TNF-alpha, and calprotectin) correlated positively with faecal IgA (p < 0.001). Probiotics tended to augment faecal IgA (p = 0.085) and significantly increased faecal alpha1-AT (p = 0.001). High intestinal IgA in early life associates with minimal intestinal inflammation and indicates reduced risk for IgE-associated allergic diseases.

Pro- and prebiotic supplementation induces a transient reduction in hemoglobin concentration in infants.

OBJECTIVES: : Regarding safety, we investigated the effect of prenatal probiotic and 6 months of pro- and prebiotic supplementation of infants on their hematologic values at 6 months and 2 years and factors affecting these values. PATIENTS AND METHODS: : In a prospective randomized controlled probiotic intervention trial in infants at high risk for allergy, we obtained blood samples consecutively from 98 infants at 6 months and from 658 children at 2 years to measure hematologic values. We collected fecal samples at 3 and 6 months to measure immunologic development by calprotectin, alpha-1-antitrypsin, tumor necrosis factor-alpha, and immunoglobulin A. RESULTS: : At 6 months, infants in the probiotic group had significantly lower hemoglobin (Hb) values than did the placebo group, mean (SD): 119.8 g/L (6.3) versus 123.3 g/L (8.4), P = 0.025. Adjustment for factors that might affect Hb values (breast-feeding duration, solid-food introduction, and sex), revealed no need for adjustment. A significant negative correlation emerged between Hb values at 6 months and fecal calprotectin at age 3 months r = -0.301, P = 0.009, which was affected neither by breast-feeding, sex, nor study group. At 2 years, hematologic values in both groups became similar. CONCLUSIONS: : Probiotics cause a gut mucosal inflammation with decreased Hb values during intervention, corrected after halting the supplementation.

Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort.

BACKGROUND: Less microbial exposure in early childhood is associated with more allergic disease later. Allergic children have a different fecal microflora, with less lactobacilli and bifidobacteria. Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation. OBJECTIVE: We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies. METHODS: In a double-blinded, placebo-controlled study we randomized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture (2 lactobacilli, bifidobacteria, and propionibacteria) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months. Infants also received a prebiotic galacto-oligosaccharide or placebo. At 5 years, we evaluated the cumulative incidence of allergic diseases (eczema, food allergy, allergic rhinitis, and asthma) and IgE sensitization. RESULTS: Of the 1018 intent-to-treat infants, 891 (88%) attended the 5-year visit. Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar: 52.6% versus 54.9% and 29.5% versus 26.6%, respectively, and 41.3% in both. No significant difference appeared in frequencies of eczema (39.3% vs 43.3%), atopic eczema (24.0% vs 25.1%), allergic rhinitis (20.7% vs 19.1%), or asthma (13.0% vs 14.1%) between groups. However, less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics (24.3% vs 40.5%; odds ratio, 0.47; 95% CI, 0.23% to 0.96%; P = .035). CONCLUSIONS: No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children. It conferred protection only to cesarean-delivered children.

Probiotics in the treatment and prevention of allergy in children.

Several fold increase in allergic diseases in developed, high-income countries during recent decades is attributed to environmental changes such as urbanization with improved hygiene. This, together with conquering severe bacterial infections during childhood, has reduced the microbial stimulation of the developing immune system of infants. Studies on the pathogenesis of allergy both in man and experimental animal have shown the importance of commensal bacteria in the gastrointestinal tract in stimulating and directing the immune system. The interest in modulating commensal bacterial flora with probiotics to prevent and treat allergy has multiplied in recent years.In the present review we report results on randomized, controlled studies in which childhood atopic eczema was treated or which aimed to prevent development of allergy during childhood.Nine studies with 639 patients have looked at the effect of probiotics in treatment of eczema. While 3 studied showed no effect, other studies suggested a moderate benefit of the use of probiotics on the severity of eczema. Studies suggested that the effect may be seen particularly in patients with food allergy and/or sensitization.Nine studies have reported on the prevention of allergy on 6 study population with altogether 1989 high risk infants. While the early study reporting the development of allergy at ages 2, 4 and 7 years showed a marked reduction of eczema in 77 treated infants, later studies have failed to show similar success. Two studies showed no effect. In the largest study with more than 900 children at age 2 atopic eczema was reduced by 20%, but at age 5 positive effect was present in only the subgroup of children who had born by cesarean section. None of studies has reported adverse effects of probiotics in infants.Result in both treatment and prevention studies are quite variable, the major reason being the use of different strains of probiotic bacteria and varying types of intervention. Even if the results are encouraging, we need a stronger effect. This may be reached by finding new strains of probiotics affecting stronger stimulation of immune system, together with longer lasting and varying treatment schedules. However, safety issues have to be observed.

Long-term safety and impact on infection rates of postnatal probiotic and prebiotic (synbiotic) treatment: randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Live probiotic bacteria and dietary prebiotic oligosaccharides (together termed synbiotics) increasingly are being used in infancy, but evidence of long-term safety is lacking. In a randomized, placebo-controlled, double-blind trial, we studied the safety and long-term effects of feeding synbiotics to newborn infants. METHODS: Between November 2000 and March 2003, pregnant mothers carrying infants at high risk for allergy were randomly assigned to receive a mixture of 4 probiotic species (Lactobacillus rhamnosus GG and LC705, Bifidobacterium breve Bb99, and Propionibacterium freudenreichii ssp shermanii) or a placebo for 4 weeks before delivery. Their infants received the same probiotics with 0.8 g of galactooligosaccharides, or a placebo, daily for 6 months after birth. Safety data were obtained from clinical examinations and interviews at follow-up visits at ages 3, 6, and 24 months and from questionnaires at ages 3, 6, 12, and 24 months. Growth data were collected at each time point. RESULTS: Of the 1018 eligible infants, 925 completed the 2-year follow-up assessment. Infants in both groups grew normally. We observed no difference in neonatal morbidity, feeding-related behaviors (such as infantile colic), or serious adverse events between the study groups. During the 6-month intervention, antibiotics were prescribed less often in the synbiotic group than in the placebo group (23% vs 28%). Throughout the follow-up period, respiratory infections occurred less frequently in the synbiotic group (geometric mean: 3.7 vs 4.2 infections). CONCLUSION: Feeding synbiotics to newborn infants was safe and seemed to increase resistance to respiratory infections during the first 2 years of life.

Increased activation of GATA-3, IL-2 and IL-5 of cord blood mononuclear cells in infants with IgE sensitization.

Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-gamma), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of beta-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.