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Background: Dietary patterns defined using principal component analysis (PCA) offer an alternative to the analysis of individual foods and nutrients and have been linked with asthma and allergic disease. However, results have not been reproducible in different settings., Objective: To identify dietary patterns common to different European countries and examine their associations with asthma and allergic symptoms., Methods: In sixteen study centers in nine European countries, 3206 individuals aged 15-77 years completed a common, internationally validated, food frequency questionnaire and a respiratory symptoms questionnaire. The outcomes of interest were current asthma, asthma symptoms score (derived based on responses to 5 asthma symptom-related questions), atopy (positive skin prick test). Spirometry was used to estimate forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), the FEV 1 /FVC, spirometric restriction (FVC below the lower limit of normal (1 /FVC < LLN. A novel meta-analytic approach was used to identify dietary patterns using PCA and to examine associations with asthma and allergic symptoms., Results: Two dietary patterns emerged, generally correlating with the same foods in different countries: one associated with intake of animal proteins and carbohydrates; the other with fruit and vegetables. There was evidence that the former pattern was associated with a higher asthma score (RR 1.63, 95% CI: 1.33-2.01), current asthma (RR 2.03, 95% CI: 1.52-2.71), wheeze (RR 1.84, 95% CI: 1.30-2.60), atopic status (RR 1.68, 95% CI: 1.16-2.44) and with decreased lung function, including an FVC

The original article [1] contained a typesetting error in Table 5; this has now been corrected.

Background: The impact of proper aspiration of nasal secretions during upper respiratory infection on the frequency and severity of symptoms of lower airways has never been investigated. The study was aimed at testing if cleaning the nasal cavities of children with recurrent wheezing using an automatic nasal aspirator improves the upper and lower respiratory symptoms during the cold season., Methods: Parents of wheezing children (age 3-72 mo.) answered questionnaires and learned using a nebulizer equipped (cases) or not equipped (controls) with an automatic nasal aspirator (DuoBaby, OMRON, Japan). During a 90-days monitoring period parents filled an electronic diary (BreathMonitor, TPS, Rome, Italy) on their child's symptoms of the upper and lower airways., Results: Eighty-nine/91 patients (43 cases, 46 controls) completed the study. Less days with upper (25.0% vs 46.4%, p = 0.004) or lower (21.8% vs 32.8%, p = 0.022) airways symptoms and less days with salbutamol inhalation (12.2% vs 16.9%, p < 0.001) were reported by cases than by controls. The episodes of upper respiratory symptoms were shorter [4.3 days (95%CI:3.8-4.9) vs 5.7 days (95%CI:5.0-6.4), p = 0.007] but not less frequent [2.3 (95%CI: 1.8-2.8) vs 2.6 (95%CI:2.2-3.0), p = 0.122] among cases than among controls. Similarly, the episodes of lower respiratory symptoms tended to be shorter [3.8 days, (95%CI: 3.4-4.2) vs 4.4 days, (95%CI: 4.4-6.0), p = 0.067] but not less frequent [1.9 (95%CI:1.5-2.3) vs 2.1 (95%CI:1.7-2.4), p = 0.240] among the group using the nasal aspirator., Conclusions: In our pilot study, the use of an automatic nasal aspirator in children with a history of recurrent wheezing was associated with an improved respiratory health during the cold season.

Background: Upper and lower airways diseases share in part their pathogenic mechanisms and frequently occur simultaneously as "United Airway Disease." Local treatment with nebulizers delivers anti-symptomatic drugs in either the upper or the lower airways, according to the particle size generated by the nebulizer. To our knowledge, no nebulizer combines both application ways. The aim of this study is to test the efficacy and usability of a new nebulizer (OMRON A3 complete), generating aerosols with particles diameters of 2-4.5 μm, 4.5-7.5 μm or >7.5 μm, according to the user's choice., Methods: Seventy-seven patients between 5 and 17 years of age with a diagnosis of rhinitis or asthma were examined. Oxymetazoline or Salbutamol were prescribed according to best clinical practice guidelines. Both drugs were administered through the OMRON A3 Complete nebulizer, with a particle dimension of >7.5 μm to treat nasal obstruction and 2-4.5 μm for bronchial obstruction. The efficacy of treatment was assessed by total nasal inspiratory airflow and FEV-1, Tiffeneau index (FEV1/FVC) and MMEF 25/75 respectively, 10 min before and after treatment. Symptom improvement and usability were measured by patients' and doctors' questionnaires., Results: Overall, 77 patients seeking care for acute respiratory symptoms were assigned to the upper (n = 39) or lower (n = 38) airways disease group. For symptoms of the upper airways, 92% (95% CI, 77-97%) of the patients reported subjective improvement, while 87% (95% CI, 73-94%) did so for the lower airways. The average total nasal inspiratory airflow improved significantly (p = 0.030) among the patients with upper airways symptoms, from 275 ml/s (95% CI, 207-342 ml/s) to 359 ml/s (95% CI, 300-419 ml/s) after Oxymetazoline administration. All selected lung function parameters (FEV1, Tiffeneau Index and MMEF25-75) significantly improved among the patients with lower airways symptoms after inhalation of Salbutamol (p < 0.001). The nebulizer was assessed as "easy to use" by over 95% of participants in both groups., Conclusions: The OMRON A3 efficiently delivers anti-symptomatic drugs in both upper and lower airways in a user-friendly way. This device may be useful to facilitate adherence to a complete treatment of respiratory symptoms in patients with symptoms of the so-called United Airway Disease.

Purpose of Review: Allergenic molecules of the house dust mite (HDM) are crucially important indoor allergens, contributing to allergic rhinitis and asthma around the globe. In the past years, recombinant molecules for diagnostics opened new pathways to investigate individual sensitization profiles and new chances for the prevention and treatment of HDM allergy. This review summarizes the latest findings on the evolution of IgE responses towards mite allergens., Recent Findings: Several cross-sectional and longitudinal studies confirmed the role of Der p 1 and Der p 2 as major allergenic proteins of the HDM. A newly identified player is the major allergen Der p 23. Apart from identifying the early sensitization towards this molecule as a risk factor for asthma in school age, a recent longitudinal study described sensitization patterns showing that the production of IgE usually starts towards a group of initiator proteins and may stay monomolecular or expand to an oligo- or even polymolecular stage. This phenomenon also correlates to clinical symptoms. A relation between a broad sensitization pattern and symptom severity has also been shown cross-sectionally. Individual sensitization profiles towards HDM allergens provide important information to evaluate a patient's current stage and risk for clinical symptoms. This knowledge paves the way for an early and adequate prevention and/or treatment.

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb-/- mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb-/- mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb-/- mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases.

Background: The evolution of the IgE response to the numerous allergen molecules of Dermatophagoides pteronyssinus is still unknown., Objectives: We sought to characterize the evolutionary patterns of the IgE response to 12 molecules of D pteronyssinus from birth to adulthood and to investigate their determinants and clinical relevance., Methods: We investigated the clinical data and sera of 722 participants in the German Multicenter Allergy Study, a birth cohort started in 1990. Diagnoses of current allergic rhinitis (AR) related to mite allergy and asthma were based on yearly interviews at the ages of 1 to 13 years and 20 years. IgE to the extract and 12 molecules of D pteronyssinus were tested by means of ImmunoCAP and microarray technology, respectively, in sera collected at ages 1, 2, 3, 5, 6, 7, 10, 13, and 20 years. Exposure to mites at age 6 and 18 months was assessed by measuring Der p 1 weight/weight concentration in house dust., Results: One hundred ninety-one (26.5%) of 722 participants ever had IgE to D pteronyssinus extract (≥0.35 kU A /L). At age 20 years, their IgE recognized most frequently Der p 2, Der p 1, and Der p 23 (group A molecules; prevalence, >40%), followed by Der p 5, Der p 7, Der p 4, and Der p 21 (group B molecules; prevalence, 15% to 30%) and Der p 11, Der p 18, clone 16, Der p 14, and Der p 15 (group C molecules; prevalence, <10%). IgE sensitization started almost invariably with group A molecules and expanded sequentially first to group B and finally to group C molecules. Early IgE sensitization onset, parental hay fever, and higher exposure to mites were associated with a broader polymolecular IgE sensitization pattern. Participants reaching the broadest IgE sensitization stage (ie, ABC) had significantly higher risk of mite-related AR and asthma than unsensitized participants. IgE to Der p 1 or Der p 23 at age 5 years or less predicted asthma at school age., Conclusions: Parental hay fever and early exposure to D pteronyssinus allergens promote IgE polysensitization to several D pteronyssinus molecules, which in turn predicts current mite-related AR and current/future asthma. These results might inspire predictive algorithms and prevention strategies against the progression of IgE sensitization to mites toward AR and asthma., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Studies of a limited number of allergens suggested that nonsensitized children produce IgG responses mainly to foodborne allergens, whereas IgE-sensitized children also produce strong IgG responses to the respective airborne molecules., Objective: We sought to systematically test the hypothesis that both the route of exposure and IgE sensitization affect IgG responses to a broad array of allergenic molecules in early childhood., Methods: We examined sera of 148 children participating in the Multicentre Allergy Study, a birth cohort born in 1990. IgG to 91 molecules of 42 sources were tested with the ImmunoCAP Solid-Phase Allergen Chip (ISAC; TFS, Uppsala, Sweden). IgE sensitization at age 2 and 7 years was defined by IgE levels of 0.35 kU A /L or greater to 1 or more of 8 or 9 extracts from common allergenic sources, respectively., Results: The prevalence and geometric mean levels of IgG to allergenic molecules in nonsensitized children were lower at age 2 years than in IgE-sensitized children, and they were extremely heterogeneous: highest for animal food (87% ± 13%; 61 ISAC Standardized Units [ISU], [95% CI, 52.5-71.5 ISU]), intermediate for vegetable food (48% ± 27%; 13 ISU [95% CI, 11.2-16.1 ISU]), and lowest for airborne allergens (24% ± 20%; 3 ISU [95% CI, 2.4-3.4 ISU]; P for trend < .001 [for percentages], P for trend < .001 [for levels]). IgG 4 antibodies were infrequent (<5%) and contributed poorly (<3%) to overall IgG antibody levels. IgG responses at age 2 years were slightly more frequent and stronger among children with than in those without IgE sensitization at age 7 years., Conclusion: The children's repertoire of IgG antibodies at 2 years of age to a broad array of animal foodborne, vegetable foodborne, and airborne allergenic molecules is profoundly dependent on the route of allergen exposure and the child's IgE sensitization status and only marginally involves the IgG 4 isotype., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The route and dose of exposure are believed to be relevant factors in the sensitization process. Pathogenesis-related group 10 protein (PR-10) molecules are a family of allergenic proteins shared by many pollens (eg, birch and alder) and foods (eg, apple, peach, and soy). Children are exposed to both pollen-derived (inhaled) and food-derived (ingested) PR-10 molecules., Objective: We sought to investigate the role of route and dose of exposure in the evolution of IgG and IgE responses to recombinant PR-10 molecules., Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990. Blood samples were collected at the ages of 1, 2, 3, 5, 6, 7, 10, and 13 years. Participants were included in the present analysis if they had (1) at least 1 serum sample at each of the 4 age periods or time points (1-3 years, 5-7 years, 10 years, and 13 years) and (2) IgE responses to birch (children with birch atopy) or no IgE response at all to 9 common aeroallergens and food allergens (nonatopic children). Therefore serum IgE antibodies to a panel of 4 airborne and 5 foodborne extracts, as well as to Bet v 1, were measured in singleplex assays, whereas IgG and IgE antibodies to a panel of 3 airborne PR-10 molecules (rBet v 1, rAln g 1, and rCor a 1.0101) and 7 foodborne PR-10 molecules (rCor a 1.0401, rMal d 1, rPru p 1, rGly m 4, rAra h 8, rApi g 1, and rDau c 1) were tested by using a multiplex microarray., Results: In the present analyses we included 28 children with birch atopy and randomly selected 28 nonatopic children from the 190 children fulfilling the inclusion criteria. Two different patterns of IgG responses to PR-10 molecules were identified. Among nonatopic subjects, a "default" IgG response was directed mostly against foodborne PR-10, started often before age 2 years, stayed weak, and was mostly transient. Among all atopic subjects, the default IgG response at age 1 year was overwhelmed after age 2 years by an "pre-atopic" IgG response, which started with or shortly before the IgE response and was intense and persistent. This atopic IgG response, as well as the IgE response, involved progressively more foodborne PR-10 proteins with frequencies and levels related to their homology with Bet v 1., Conclusions: The results suggest that children have a default antibody response to PR-10 molecules, which is early, weak, and transient; does not involve IgE; and is initiated by foodborne PR-10. By contrast, an atopic antibody response to PR-10 molecules is delayed, strong, and persistent; involves both IgG and IgE; and is initiated by airborne PR-10., (Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Complex multifactorial diseases such as allergic rhinitis and asthma are not only becoming an increasing burden to healthcare systems, but especially affect the life quality of children and families suffering from their allergic symptoms. Also physicians are challenged by the multifaceted diseases as their work involves not only the often difficult decisions on case-adapted diagnostics, treatment, and monitoring, but also possible preventive measures. This review gives an outline of the latest scientific developments related to the etiology, diagnosis, and management of allergic airway diseases in childhood, as well as prenatal and early life risk factors and strategies for prevention., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: An early IgE response to grass or birch pollen can anticipate seasonal allergic rhinitis to pollen later in life or remain clinically silent., Objective: To identify risk factors early in life that allow discriminating pathogenic from non-pathogenic IgE responses and contribute to the development of seasonal allergic rhinitis to grass pollen., Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was yearly administered and blood samples collected at age 1,2,3,5,6,7,10,13 yr. The definition of the primary outcome grass- and birch-pollen-related seasonal allergic rhinitis (SARg, SARb) was based on nasal symptoms in June/July and April, respectively. Serum IgE antibodies to Phleum pratense and Betula verrucosae extracts were monitored with immune-enzymatic singleplex assays., Results: Of the 820 examined children, 177 and 148 developed SARg and SARb, respectively. Among healthy children aged 3 or more years, IgE to grass pollen was the strongest risk factor of SARg (OR 10.39, 95%CI 6.1-17.6, p < 0.001), while parental hay fever was the only risk factor in early childhood independently associated with future SARg (1 parent: OR 2.56, 95%CI 1.4-4.5, p < 0.001; 2 parents: OR 4.17, 95%CI 1.7-10.1) and SARb (1 parent OR: 5.21, 95%CI 2.20-12.4, p < 0.001; 2 parents: OR 8.02, 95%CI 2.0-32.9, p < 0.001). Parental hay fever was associated with an increase of the concentration of pollen-specific IgE in seropositive subjects, after the age of 6 and was also a hallmark of molecularly more complex specific IgE responses to grass or birch pollen at age 6 or older., Conclusions: Parental hay fever and specific IgE to grass and/or birch pollen are strong pre-clinical determinants and potentially good predictors of seasonal allergic rhinitis., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Allergen-specific IgG antibodies play a significant role in allergen-specific tolerance, either naturally induced or generated by specific immunotherapy. Nevertheless, the underlying mechanisms are still debated, and allergen-specific IgG determinations are not recommended as a diagnostic tool in IgE-mediated allergy. This review summarizes the latest findings on the immunological and diagnostic role of IgG antibodies in respiratory and food allergies, and during allergen-specific immunotherapy.

In the past years, a wide range of epidemiological, clinical, and experimental studies have produced remarkable advances in the field of respiratory allergies in childhood. By the recent investigations on epidemiological trends, risk factors, and prevention of asthma and allergic rhinitis, various exiting concepts have been challenged, and novel innovative approaches have been developed. Pediatric Allergy and Immunology (PAI), with a number of highly relevant contributions between 2010 and 2012, has become an important forum in this area. The prevalence of asthma in some developed countries may have reached a plateau, while in developing countries, where the prevalence was previously low, allergic diseases are still on the increase. A wide array of risk and protective factors, including hygiene, infections, outdoor and indoor air pollution, allergen exposure, breast-feeding practices, nutrition, and obesity, play a multifaceted role in shaping the observed worldwide trends of respiratory allergies. Under the guidance of recent research, prediction and prevention strategies in the clinical practice are progressively changing, the focus moving away from avoidance of allergen exposure and toward tolerance induction., (© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.)

Background: IgE sensitization against grass pollen is a cause of seasonal allergic rhinitis., Objective: We sought to investigate the evolution at the molecular level and the preclinical predictive value of IgE responses against grass pollen., Methods: The German Multicentre Allergy Study examined a birth cohort born in 1990. A questionnaire was administered yearly, and blood samples were collected at 1, 2, 3, 5, 6, 7, 10, and 13 years of age. Grass pollen-related seasonal allergic rhinitis (SARg) was diagnosed according to nasal symptoms in June/July. Serum IgE antibodies to Phleum pratense extract and 8 P pratense molecules were tested with immune-enzymatic singleplex and multiplex assays, respectively., Results: One hundred seventy-seven of the 820 examined children had SARg. A weak monomolecular/oligomolecular IgE response to P pratense was observed very frequently before SARg onset. These initial IgE responses increased in concentration and molecular complexity during the preclinical and clinical process. A typical progression of IgE sensitization was observed: Phl p 1 (initiator in >75% of cases); then Phl p 4 and Phl p 5; then Phl p 2, Phl p 6, and Phl p 11; and then Phl p 12 and Phl p 7. At age 3 years, IgE sensitization predicted SARg by age 12 years (positive predictive value, 68% [95% CI, 50% to 82%]; negative predictive value, 84% [95% CI, 80% to 87%]). At this preclinical prediction time, the number of recognized molecules and the serum levels of IgE to P pratense were significantly lower than at 3 or more years after SARg onset., Conclusions: The IgE response against grass pollen molecules can start years before disease onset as a weak monosensitization or oligosensitization phenomenon. It can increase in serum concentration and complexity through a "molecular spreading" process during preclinical and early clinical disease stages. Testing IgE sensitization at a preclinical stage facilitates prediction of seasonal allergic rhinitis at its molecular monosensitization or oligosensitization stage., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)