Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

BACKGROUND: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms). AIMS: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. METHODS: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. RESULTS: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. CONCLUSIONS: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

High IgE levels to α-lactalbumin, ß-lactoglobulin and casein predict less successful cow's milk oral immunotherapy.

BACKGROUND: A new treatment option for persistent cow's milk allergy (CMA) is oral immunotherapy (OIT). Not all patients develop tolerance during therapy, and markers to identify those who will benefit from it are needed. The objective was to study the IgE and IgG4 antibody profiles to milk and milk proteins before and after OIT in relation to clinical outcome. METHODS: Seventy-six children (5-17 years) with challenge-verified CMA were subjected to a 6-month OIT protocol. The treatment aimed at reaching a maintenance dose of 200 ml CM (high dose = HD). Those who did not reach target were analysed as a low-dose (LD) group. Sera were characterized before and after OIT regarding serum levels of IgE and IgG4 to milk and five milk allergen components evaluated together with clinical CMA symptoms and outcome of OIT. RESULTS: Fifty-five (72%) patients reached the maintenance dose (HD) during therapy. High specific IgE levels towards the milk allergens α-lactalbumin (P = 0.048), ß-lactoglobulin (P = 0.006) and casein (P = 0.015) before OIT start were associated with lower maintenance dose reached. Patients who developed desensitization had a larger increase in IgG4 levels to α-lactalbumin (P = 0.034), ß-lactoglobulin (P = 0.010), casein (P = 0.047) and lactoferrin (P = 0.030) during treatment than those who failed. CONCLUSIONS: Component-resolved diagnostics before OIT can help to identify children with lower probability of a successful OIT outcome, as high IgE levels to α-lactalbumin, ß-lactoglobulin and casein are associated with lower maintenance dose reached. An increase in the IgG4 concentration to milk components during treatment indicated effective desensitization.

Wheat allergy in children - new tools for diagnostics.

BACKGROUND: The detection of wheat-specific IgE in children often leads to a suspicion of wheat allergy, but little information is available on the most reliable wheat allergens for predicting clinical reactivity. OBJECTIVE: To evaluate the role of allergenic components of wheat in wheat allergy diagnostics. METHODS: One hundred and eight children (median age 1.5 years; range 0.6-17.3 years) with suspected wheat allergy underwent open or double-blinded, placebo-controlled oral wheat challenges. Responsiveness to different allergenic components of wheat was studied by skin prick tests and by determination of serum IgE antibodies using a semi-quantitative microarray assay. RESULTS: Thirty (28%) children reacted with immediate symptoms, and 27 (25%) with delayed symptoms to ingested wheat, whereas 51 (47%) children exhibited no reactions in oral wheat challenges. Positive IgE responses to any of the 12 allergenic components of wheat was seen in 93%, 41%, and 43% of those with immediate, delayed or no reactions to ingested wheat, respectively (P < 0.001 to P < 0.05 in every comparisons between those with immediate reactions and those with no reactions). Positive IgE responses to ≥5 different allergenic components improved significantly the diagnostic accuracy (with a positive likelihood ratio (LR+) of 5.10). Alpha-amylase inhibitors (AAI), in particular dimeric AAI 0.19 (LR+ 6.12), alpha-, beta-, and gamma-gliadins (LR+ from 3.57 to 4.53), and high-molecular-weight (HMW) glutenin subunits (LR+ 4.37) were the single allergenic components of wheat differentiating most effectively those with immediate symptoms from those who did not exhibit any reactions. CONCLUSIONS AND CLINICAL RELEVANCE: Wheat allergy diagnostics is difficult, even using sophisticated component methods. Our results confirm earlier findings about gliadins and identify the dimeric AAI 0.19, as a relevant allergen in clinically reactive patients when compared to non-reactive subjects. The accuracy of wheat allergy diagnosis may be improved by measuring IgE responses to several components of wheat.

Intestinal defensin secretion in infancy is associated with the emergence of sensitization and atopic dermatitis.

BACKGROUND: Intestinal flora and innate immunity, and their interactions impact adaptive immunity. OBJECTIVE: To study the association of fecal defensin levels in infancy with synbiotic treatment and with the emergence of atopy. METHODS: The randomly selected group of 102 infants belonged to a randomized, double-blind placebo-controlled trial where 1223 infants in high risk for allergy received, from birth to 6 months, a mixture of synbiotics, or placebo. Clinical trials registration number for the clinical trial is NCT00298337. In the subgroup, 45 received active treatment and 56 received placebo treatment. Follow-up for the emergence of sensitization and allergic diseases lasted 5 years. At the age of 3 (n = 96) and 6 (n = 87) months, we measured fecal levels of human neutrophil peptide (HNP) 1-3 and of ß-defensin 2 (HBD2) using enzyme linked immunosorbent assays and concentrations of lactic acid bacteria on MRS agar. We used multifactorial regression in data analysis. RESULTS: Fecal levels of HNP1-3 and HBD2 decreased from the age of 3-6 months (P < 0.0001). HBD2 levels decreased less in the synbiotics group compared with placebo (P < 0.02). High fecal HBD2 levels at 6 months were associated with an increased risk for sensitization by the age of 5 years (OR 2.5, 95% confidence interval 1.1-5.8, P < 0.03). High fecal HNP1-3 levels at 6 months were associated with a decreased risk for atopic dermatitis (OR 0.4, 95% CI 0.1-1.0, P < 0.05). Samples with very low or high HBD2 levels at 6 months had low concentrations of lactic acid bacteria (P < 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Early innate immunity responses in the gut are associated with the emergence of sensitization and atopic dermatitis later in childhood.

Ovalbumin-specific immunoglobulins A and G levels at age 2 years are associated with the occurrence of atopic disorders.

BACKGROUND: Humoral responses to food antigens may reflect the propensity of a child's immune system to develop tolerance to innocuous antigens. Early nutrition as well as probiotics may influence these immunological responses. OBJECTIVE: To study the association of humoral responses to early food antigens with the administration of prebiotics and probiotics, with the occurrence of allergy, and with the length of exclusive breastfeeding. METHODS: In a randomized double-blind allergy prevention trial in high-risk children, 1018 mothers took probiotics or placebo from the 36th week of gestation, and their newborn infants received probiotics and prebiotics or placebo during 6 months. At 2 and 5 years, we evaluated the cumulative incidence of allergic diseases (food allergy, eczema, asthma, rhinitis) and sensitization (skin prick test ≥3 mm or serum antigen-specific IgE>0.7 kU/L). In 688 infants at age 2, we measured in sera-specific IgA, IgG, IgG1, and IgG4 antibody levels to cow's milk (CM), α-casein (CAS), ß-lactoglobulin (BLG), and ovalbumin (OVA) with ELISA, and specific IgE levels to CM and hen's egg with UniCap. RESULTS: Probiotic treatment (n=342) compared with placebo (n=346) showed no effect on serum food-specific IgA, IgG, IgG1, or IgG4 concentrations at age 2. Atopic children had higher OVA-IgA (P<0.001), OVA-IgG (P=0.001), OVA-IgG1 (P<0.001), and egg-IgE but lower OVA-IgG4/egg-IgE ratio (P<0.001) than non-atopic children. Longer duration of exclusive breastfeeding (≥4 vs. <4 months) was associated with reduced CM- and CAS-specific serum IgA (P<0.001) and IgG levels (P<0.001; P=0.003). CONCLUSION AND CLINICAL RELEVANCE: Allergy was associated with more intense IgA and IgG responses to OVA. Breastfeeding depressed humoral responses, whereas prebiotics and probiotics supplementation showed no immunomodulatory effect. The effect of probiotics on allergies is not mediated through food-specific antibody responses. Furthermore, OVA-specific IgA and IgG antibodies may help in assessing the risk for atopy.

Probiotics in infancy induce protective immune profiles that are characteristic for chronic low-grade inflammation.

BACKGROUND: Probiotics are widely studied both in the treatment and prevention of allergic diseases, but their mode of action is poorly known. OBJECTIVE: Our aim was to examine the effect of probiotic bacteria on in vivo cytokine, antibody, and inflammatory responses in allergy-prone infants. METHODS: In a randomized double-blind study, probiotic bacteria or placebo were given for 1 month before delivery to mothers and for 6 months to infants with a family history of allergy. Plasma samples were analysed for C-reactive protein (CRP), total IgA and IgE, food-specific IgA, IgG, and IgE, IL-2, IL-4, IL-6, IL-10, TNF-alpha, and IFN-gamma. We analysed the associations of immunological and inflammatory parameters at age 6 months with probiotic treatment and allergic phenotype at 2 years. RESULTS: Infants receiving probiotic bacteria had higher plasma levels of CRP (P=0.008), total IgA (P=0.016), total IgE (P=0.047), and IL-10 (P=0.002) than infants in the placebo group. Increased plasma CRP level at age 6 months was associated with a decreased risk of eczema [odds ratio (OR) 0.41 [95% confidence interval (CI) 0.17-0.99], P=0.046], and with a decreased risk of allergic disease [OR 0.38 (95% CI 0.16-0.87), P=0.023] at age 2 years, when adjusted with probiotic use. CONCLUSION: The association of CRP with a decreased risk of eczema at 2 years of age in allergy-prone children supports the view that chronic, low-grade inflammation protects from eczema. Probiotic-induced low-grade inflammation was characterized by elevation of IgE, IgA, and IL-10, the changes typically observed in helminth infection-associated induction of regulatory mechanisms. The findings emphasize the role of chronic microbial exposure as an immune modulator protecting from allergy.

Childhood BMI in relation to microbiota in infancy and lifetime antibiotic use.

BACKGROUND: Children with high body mass index (BMI) at preschool age are at risk of developing obesity. Early identification of factors that increase the risk of excessive weight gain could help direct preventive actions. The intestinal microbiota and antibiotic use have been identified as potential modulators of early metabolic programming and weight development. To test if the early microbiota composition is associated with later BMI, and if antibiotic use modifies this association, we analysed the faecal microbiota composition at 3 months and the BMI at 5-6 years in two cohorts of healthy children born vaginally at term in the Netherlands (N = 87) and Finland (N = 75). We obtained lifetime antibiotic use records and measured weight and height of all children. RESULTS: The relative abundance of streptococci was positively and the relative abundance of bifidobacteria negatively associated with the BMI outcome. The association was especially strong among children with a history of antibiotic use. Bacteroides relative abundance was associated with BMI only in the children with minimal lifetime antibiotic exposure. CONCLUSIONS: The intestinal microbiota of infants are predictive of later BMI and may serve as an early indicator of obesity risk. Bifidobacteria and streptococci, which are indicators of microbiota maturation in infants, are likely candidates for metabolic programming of infants, and their influence on BMI appears to depend on later antibiotic use.

Anaerobically digested poultry slaughterhouse wastes as fertiliser in agriculture.

Chemical and physical analysis, 27-d plant growth assays with carrot (Daucus carota) and Chinese cabbage (Brassica campestris var. chinensis), and 5-d phytotoxicity assays with Chinese cabbage and perennial ryegrass (Lolium perenne) were used to investigate the suitability of anaerobically digested poultry slaughterhouse waste for fertiliser in agriculture and the effect of aerobic post-treatment on the properties of the digested material. The digested material appeared to be rich in nitrogen. In 27-d assays with digested material as nitrogen source, carrots grew almost as well as those fertilised with a commercial mineral fertiliser used as reference, whereas, the growth of Chinese cabbage was inhibited. In further 5-d phytotoxicity assays, the digested material inhibited the germination and root growth of ryegrass and Chinese cabbage, apparently because of organic acids present in it. Aerobic post-treatment of the material reduced its phytotoxicity but, probably due to the volatilisation of ammonia, resulted in loss of nitrogen.

Do Highways Influence Density of Land Birds?

/ Land bird densities in roadside habitats were studied in 17 locations in central Finland by the line transect method. Two transects were censused in each location. The first transect was situated 25 m from highway edge and the second transect 200 m away from the first one. The results suggested that land bird density was lower closer to highways. Species that avoided the road included willow warbler (Phylloscopus trochilus), crossbills (Loxia spp.), and tree pipit (Anthus trivialis). The composition of the bird community did not vary significantly between the compared transects. Some species appeared to favour road-forest edges but this could not be confirmed with our data. These species were not the same as have been reported to favor clear-fellings-mature forest edges. Therefore, the edge effect does not seem to be the most important factor controlling relative bird densities immediately adjacent and further away from highways. The likelihood of avoiding the problems the highways are causing for bird density are been discussed.KEY WORDS: Highways; Infrastructure; Bird density; Landscape ecology

Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial.

BACKGROUND: Probiotic bacteria are suggested to reduce symptoms of the atopic eczema/dermatitis syndrome (AEDS) in food-allergic infants. We aimed to investigate whether probiotic bacteria have any beneficial effect on AEDS. METHODS: Follow-up of severity of AEDS by the Severity Scoring of Atopic Dermatitis (SCORAD) index in 230 infants with suspected cow's milk allergy (CMA) receiving, in a randomized double-blinded manner, concomitant with elimination diet and skin treatment, Lactobacillus GG (LGG), a mixture of four probiotic strains, or placebo for 4 weeks. Four weeks after the treatment, CMA was diagnosed with a double-blind placebo-controlled (DBPC) milk challenge in 120 infants. RESULTS: In the whole group, mean SCORAD (at baseline 32.5) decreased by 65%, but with no differences between treatment groups immediately or 4 weeks after the treatment. No treatment differences were observed in infants with CMA either. In IgE-sensitized infants, however, the LGG group showed a greater reduction in SCORAD than did the placebo group, -26.1 vs-19.8 (P=0.036), from baseline to 4 weeks after the treatment. Exclusion of infants who had received antibiotics during the study reinforced the findings in the IgE-sensitized subgroup. CONCLUSION: Treatment with LGG may alleviate AEDS symptoms in IgE-sensitized infants but not in non-IgE-sensitized infants.

Allergenicity of cow milk proteins.

The allergenicity and antigenicity of cow milk proteins are age dependent. Because the nonspecific and specific factors inhibiting the passage of cow milk proteins through the epithelial layer of the intestine are deficient at birth, although developing during early infancy, allergy to cow milk may be acquired during the first year of life. Allergic reactivity to cow milk is lost during childhood in the vast majority of cases. This change may depend at least partly on the development of the local immune system of the gut producing antigen-specific IgA antibodies. Circulating IgG antibodies to cow milk proteins are always produced when an infant has cow milk in the diet but are not associated with allergy; their titer is reduced with age. Clinical challenge tests show that most cow milk-allergic patients react to several protein fractions of cow milk. A patient may have IgE antibodies to several fractions of cow milk, measured either by skin testing or by radioallergosorbent test. Likewise, various tests for cell-mediated immunity may show positive reactions to several fractions. No single major allergen is apparent in cow milk, according to either the challenge tests or laboratory procedures: casein, alpha-lactalbumin, and beta-lactoglobulin all show a high proportion of positive reactions.

Mucosal IgA, mucosal cow's milk antibodies, serum cow's milk antibodies and gastrointestinal permeability in infants.

We have studied development of the levels of IgA cow's milk (CM) antibodies in the saliva, faeces and serum of 20 term and 20 preterm infants from birth to 8 months. All infants already had IgA in their saliva during the first week of life. The levels peaked at the age of one month, thereafter decreasing in both groups; from the age of three months levels remained stable. Term infants had higher levels than preterm infants, but no differences were found between breastfed and CM-fed infants. Breast-fed infants had higher levels of IgA in their faeces than did CM-fed infants; the IgA levels were similar in breast-fed term and preterm infants, being highest at birth, and decreasing thereafter. We also showed rising titers of serum IgA CM antibodies, with higher levels in infants regularly exposed to CM than in breast-fed infants. We sought associations between the magnitude of intestinal permeability to human alpha-lactalbumin (ALA) measured at the ages of 4-7 days and one month and the levels of IgG antibodies to CM, but no such relation was found.

Gut permeability to human alpha-lactalbumin, beta-lactoglobulin, mannitol, and lactulose in celiac disease.

Our objective was to examine the permeability of the gut to protein macromolecules and sugar probes and their possible association in celiac disease patients. We studied the permeability to human alpha-lactalbumin, beta-lactoglobulin, mannitol, and lactulose on 46 occasions in 33 celiac disease patients in various phases of the disease; in addition, mannitol and lactulose permeability was studied in 18 healthy controls. Lactalbumin absorption was detected in 19 of 42 patients tested, more often in celiac disease patients with villous atrophy than in those with normal jejunal biopsy (p = 0.01). Higher absorption of lactalbumin was found in patients with subtotal villous atrophy than in those with normal biopsy (p = 0.02). beta-lactoglobulin was found in four of 42 patients tested. Less mannitol was absorbed by patients with either subtotal or partial villous atrophy than by those with normal histology (p = 0.001 and 0.006, respectively). Lactulose recovery was higher in newly diagnosed patients and patients with subtotal villous atrophy than in controls (p = 0.007 and 0.03, respectively). The lactulose/mannitol ratio was higher in newly diagnosed patients and patients with villous atrophy than in controls (p = 0.002 and 0.002, respectively). The correlation between permeability to lactalbumin and mannitol and lactulose was poor. We conclude that permeability to proteins and sugar molecules is abnormal in celiac disease patients with mucosal damage and that they probably reflect different mechanisms of penetration.

Human alpha-lactalbumin and bovine beta-lactoglobulin absorption in infants.

We investigated gut permeability to human alpha-lactalbumin (ALA) and bovine beta-lactoglobulin (BLG) in 20 infants from birth to 8 months or until weaning, before which they were on a strictly cow's-milk-free diet. We measured the proteins with a sensitive, solid-phase, double-sandwich immunofluorometric assay. Median (range) levels of serum ALA on days 3-4 after birth, and at 1 and 2 months of age were 31 (12-225), 6 (0-55), and 2 (0-16) micrograms/l serum per g ALA given per kg body weight, respectively. At 3, 5, and 8 months of age, only trace amounts of ALA were found. One week after weaning, serum BLG was found in 5/13 infants (38%) and at 2 weeks in 3/14 infants (21%), with median concentrations of 7 and 4 micrograms/l serum per g BLG given per kg body weight, respectively. No ALA could be detected in any of these samples. In absorption of ALA, the four infants who had allergic symptoms did not differ from those without symptoms. Thus, systemic absorption of ALA and BLG does occur in infants. Absorption of ALA is greatest after birth, when 3 x 10(-4) (median) of the given antigens are absorbed, but absorption decreases rapidly. The gut may often be transiently permeable to BLG when cow's-milk-based formula is started.

Gas chromatographic properties of the M series of universal retention index standards and their application to pesticide analysis.

The suitability of alkylbis(trifluoromethyl)phosphine sulphides for use as universal retention-index standards has been confirmed. In routine work, the M series were detected at the level of 0.4-0.6 pmol with flame ionization detection (FID), 2-7 fmol with alkaline thermionization detection (ATD) and 3-5 fmol with electron-capture detection (ECD). The sensitivities of ATD and ECD are so much greater than that of FID that their simultaneous use with FID is not possible. The sensitivities of ECD and ATD are similar enough that parallel use is possible. Examples of two-channel retention-index monitoring of pesticides from real samples are given.

Behavioural responses of Eurasian treecreepers, Certhia familiaris, to competition with ants

Competition for a specific resource that is essential for the survival of both the competitors may be intense even between very dissimilar taxa. However, the importance of the effects caused by such interspecific competition has seldom been emphasized. These effects can appear as differences in individual foraging behaviour during the breeding season, which can result in critical variation in fitness. In this study we examined the effects of wood ants (Formica rufa group) on the abundance of other invertebrates on tree trunks and on the foraging site selection of breeding Eurasian treecreepers, which use the same habitat as wood ants. Arthropods were scarcer on the trunks with ants present; the treecreepers avoided these trunks and foraged for a shorter time on trunks with ants than on trunks without ants. We also tested experimentally the existence of competition between ants and treecreepers by comparing the foraging behaviour of breeding treecreepers on spruce trunks with ants, without ants and with experimentally reduced numbers of ants. On average arthropods were scarcest on trunks with ants present. Male treecreepers also foraged for a shorter time on spruce trunks with ants. The reduction in ant numbers allowed food resources on trunks to recover over a week and led to longer foraging times of the treecreepers on these trunks than on trunks with ants present. The longest treecreeper visits were on trunks without ants. Our results suggest that competition between two very different taxa may be effective in determining the behaviour of foraging individuals.Copyright 1997 The Association for the Study of Animal Behaviour1997The Association for the Study of Animal Behaviour

Breastfeeding and allergic disease: a multidisciplinary review of the literature (1966-2001) on the mode of early feeding in infancy and its impact on later atopic manifestations.

BACKGROUND: Strategies to prevent children from developing allergy have been elaborated on the basis of state-of-the-art reviews of the scientific literature regarding pets and allergies, building dampness and health, and building ventilation and health. A similar multidisciplinary review of infant feeding mode in relation to allergy has not been published previously. Here, the objective is to review the scientific literature regarding the impact of early feeding (breast milk and/or cow's milk and/or formula) on development of atopic disease. The work was performed by a multidisciplinary group of Scandinavian researchers. METHODS: The search in the literature identified 4323 articles that contained at least one of the exposure and health effect terms. A total of 4191 articles were excluded mainly because they did not contain information on both exposure and health effects. Consequently, 132 studies have been scrutinized by this review group. RESULTS: Of the 132 studies selected, 56 were regarded as conclusive. Several factors contributed to the exclusions. The studies considered conclusive by the review group were categorized according to population and study design. CONCLUSIONS: The review group concluded that breastfeeding seems to protect from the development of atopic disease. The effect appears even stronger in children with atopic heredity. If breast milk is unavailable or insufficient, extensively hydrolysed formulas are preferable to unhydrolysed or partially hydrolysed formulas in terms of the risk of some atopic manifestations.