Development and preliminary validation of a new screening questionnaire for identifying atopic children

Background: Allergic diseases represent a frequent and increasing condition affecting children. A screening questionnaire allowing an easy identification of children with symptoms of allergic diseases may improve management and clinical outcome. The aim of this study was to develop and validate an easy-to-use screening questionnaire to detect children requiring further allergological evaluations. Methods: A 10-item questionnaire, evaluating the presence and the history of the most frequent allergic conditions affecting children, including allergic asthma, allergic rhinitis and conjunctivitis, food allergy, and atopic dermatitis, was developed and administered to 214 parents of children from 5 to 10 years of age (163 with allergic disease and 51 healthy, nonallergic children). Validation was performed by Pearson's correlation between the clinical diagnosis and the responses to the questionnaire. Internal consistency was computed by Cronbach's alpha correlation coefficient. Sensitivity and specificity of the novel questionnaire were assessed by the receiver operating characteristic (ROC) curve. Results: Validation analysis of the new children atopy (ChAt) questionnaire showed good internal consistency with a Cronbach's alpha of 0.757. Responses to the items evaluating the presence of individual allergic conditions significantly correlated with the clinical diagnosis (p<0.001). The ROC curve showed an area of 0.956 and identified a cutoff value >2 of the ChAt questionnaire total score for detection of allergy (sensitivity =0.92 and specificity =0.902). Conclusion: The novel ChAt questionnaire represents a simple tool able to detect the presence of all major allergic diseases in a pediatric population allowing an early identification of allergic multimorbidity and potentially facilitating clinical management

The effect of residential urban greenness on allergic respiratory diseases in youth: A narrative review

Background: Environmental exposures across the life course may be a contributor to the increased worldwide prevalence of respiratory and allergic diseases occurring in the last decades. Asthma and rhinoconjunctivitis especially contribute to the global burden of disease. Greenness has been suggested to have beneficial effects in terms of reduction of occurrence of allergic respiratory diseases. However, the available evidence of a relationship between urban greenness and childhood health outcomes is not yet conclusive. The current review aimed at investigating the current state of evidence, exploring the relationship between children's exposure to residential urban greenness and development of allergic respiratory diseases, jointly considering health outcomes and study design. Methods: The search strategy was designed to identify studies linking urban greenness exposure to asthma, rhinoconjunctivitis, and lung function in children and adolescents. This was a narrative review of literature following PRISMA guidelines performed using electronic search in databases of PubMed and Embase (Ovid) from the date of inception to December 2018. Results: Our search strategy identified 2315 articles; after exclusion of duplicates (n = 701), 1614 articles were screened. Following review of titles and abstracts, 162 articles were identified as potentially eligible. Of these, 148 were excluded following full-text evaluation, and 14 were included in this review. Different methods for assessing greenness exposure were found; the most used was Normalized Difference Vegetation Index. Asthma, wheezing, bronchitis, rhinoconjunctivitis, allergic symptoms, lung function, and allergic sensitization were the outcomes assessed in the identified studies; among them, asthma was the one most frequently investigated. Conclusions: The present review showed inconsistencies in the results mainly due to differences in study design, population, exposure assessment, geographic region, and ascertainment of outcome. Overall, there is a suggestion of an association between urban greenness in early life and the occurrence of allergic respiratory diseases during childhood, although the evidence is still inconsistent. It is therefore hard to draw a conclusive interpretation, so that the understanding of the impact of greenness on allergic respiratory diseases in children and adolescents remains difficult

The discovery of potent, selective, and reversible inhibitors of the house dust mite peptidase allergen Der p 1: an innovative approach to the treatment of allergic asthma.

Blocking the bioactivity of allergens is conceptually attractive as a small-molecule therapy for allergic diseases but has not been attempted previously. Group 1 allergens of house dust mites (HDM) are meaningful targets in this quest because they are globally prevalent and clinically important triggers of allergic asthma. Group 1 HDM allergens are cysteine peptidases whose proteolytic activity triggers essential steps in the allergy cascade. Using the HDM allergen Der p 1 as an archetype for structure-based drug discovery, we have identified a series of novel, reversible inhibitors. Potency and selectivity were manipulated by optimizing drug interactions with enzyme binding pockets, while variation of terminal groups conferred the physicochemical and pharmacokinetic attributes required for inhaled delivery. Studies in animals challenged with the gamut of HDM allergens showed an attenuation of allergic responses by targeting just a single component, namely, Der p 1. Our findings suggest that these inhibitors may be used as novel therapies for allergic asthma

Divergent functions for airway epithelial matrix metalloproteinase 7 and retinoic acid in experimental asthma.

The innate immune response of airway epithelial cells to airborne allergens initiates the development of T cell responses that are central to allergic inflammation. Although proteinase allergens induce the expression of interleukin 25, we show here that epithelial matrix metalloproteinase 7 (MMP7) was expressed during asthma and was required for the maximum activity of interleukin 25 in promoting the differentiation of T helper type 2 cells. Allergen-challenged Mmp7(-/-) mice had less airway hyper-reactivity and production of allergic inflammatory cytokines and higher expression of retinal dehydrogenase 1. Inhibition of retinal dehydrogenase 1 restored the asthma phenotype of Mmp7(-/-) mice and inhibited the responses of lung regulatory T cells, whereas exogenous administration of retinoic acid attenuated the asthma phenotype. Thus, MMP7 coordinates allergic lung inflammation by activating interleukin 25 while simultaneously inhibiting retinoid-dependent development of regulatory T cells

Hydrolysed formula and risk of allergic or autoimmune disease: a systematic review and meta-analysis

Objective To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. Design Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. Data sources Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. Eligibility criteria for selecting studies Prospective intervention trials of hydrolysed cows’ milk formula compared with another hydrolysed formula, human breast milk, or a standard cows’ milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. Results 37 eligible intervention trials of hydrolysed formula were identified, including over 19 000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows’ milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I2=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I2=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I2=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows’ milk. Conclusion These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants

Low Baseline Pneumococcal Antibody Titers Predict Specific Antibody Deficiency, Increased Upper Respiratory Infections, and Allergy Sensitization.

Background:Inadequate titers of pneumococcal antibody (PA) are commonly present among patients with recurrent respiratory infections. Objective:We sought to determine the effect of the degree of inadequacy in baseline PA titers on the subsequent polysaccharide vaccine response, the incidence of sinusitis, and allergic conditions. Methods:A total of 313 patients aged 6 to 70 years with symptoms of recurrent respiratory infections were classified by baseline-pPA (percentage of protective [≥1.3 µg/mL] PA serotypes/total tested serotypes) and postvaccination pPA (post-pPA): Group A (adequate baseline-pPA), Group B (inadequate baseline-pPA, adequate post-pPA, responders), and Group C (inadequate baseline-pPA, inadequate postpPA, nonresponders, specific antibody deficiency [SAD]). Immunity against Streptococcus pneumoniae was defined as adequate when the pPA was ≥70%. Each group and combined groups, Group AB (inadequate baseline-pPA), and Group BC (adequate post-pPA) were analyzed for demographics, history of sinusitis, recurrent sinusitis in the following year, allergic conditions, and association with inadequate individual serotype titers. Results:Over 80% of patients with respiratory symptoms had inadequate baseline-pPA. Baseline-pPA and SAD prevalence are inversely related (odds ratio = 2.02, 95% CI: 1.15-3.57, P = .01). Inadequate serotype 3 antibody titer is highly associated with SAD (odds ratio = 2.02, 96% CI: 1.61-5.45, P < .01). The groups with inadequate pPA (Group B and C, or BC) had significantly higher percentage of patients with chronic rhinosinusitis (P < .001), allergic sensitization, and allergic rhinitis (P < .05). Group A contained higher percentage of patients with recurrent upper airway infections (P < .001). Conclusion:Low baseline-pPA and low antibody titers to serotype 3 are highly associated with SAD, increased incidence of respiratory infections including CRS and allergic conditions