The natural history of peanut sensitization and allergy in a birth cohort

Information on the natural history of peanut-induced allergic sensitization (PAS) and clinical peanut allergy (PA) remains limited. Most previous studies selected children who were given a diagnosis of PA, which does not provide the population perspective and probably ignores those with low levels of sensitization.1,2 There are no population-based studies on the natural history of PAS or PA. To provide a population perspective, we used the Isle of Wight birth cohort (n = 1456) and determined the natural history of PAS and PA, focusing on incidence, persistence, and remission

The natural history of peanut sensitization and allergy in a birth cohort

Information on the natural history of peanut-induced allergic sensitization (PAS) and clinical peanut allergy (PA) remains limited. Most previous studies selected children who were given a diagnosis of PA, which does not provide the population perspective and probably ignores those with low levels of sensitization.1,2 There are no population-based studies on the natural history of PAS or PA. To provide a population perspective, we used the Isle of Wight birth cohort (n = 1456) and determined the natural history of PAS and PA, focusing on incidence, persistence, and remission

Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood: findings from 2 Isle of Wight birth cohorts’ 12-years apart

Background: While the prevalence of asthma in children is decreasing or remaining the same, time-trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence.Objective: To assess time -trends of wheeze, rhinitis and aero-allergen sensitisation prevalence at 10 years of age we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence we assessed association of family-history, early life exposures and sensitisation with wheeze and rhinitis in each cohort.Methods: The IoW (Isle-of-Wight) and FAIR (Food-Allergy-and-Intolerance-Research) unselected birth cohorts were established in 1989 and 2001 in IoW. Identical ISAAC questionnaire and Skin Prick test data were collected and compared at 10 years of age.Results: Over the 12 year period from 2001 to 2012, prevalence of lifetime-wheeze, current-wheeze, and those ever-treated-for-asthma decreased by 15.9% (45.5-vs-29.6,p<0.001), 3.9% (18.9-vs-15, p=0.020) and 8.2% (31.7-vs-23.5, p=0.001) respectively. Conversely, current-rhinitis and lifetime-rhinitis prevalence increased by 5.5% (22.6-vs-28.1, p=0.004) and 13% (18.6-vs-31.7, p<0.001) respectively. Atopic status remained stable, however house dust mite (HDM) sensitisation decreased by 5.6% (19.2-vs-13.6, p=0.004) and grass sensitisation increased by 3.5% (12.9-vs-16.4, p=0.054). Male-sex, parental history of asthma and HDM sensitisation were significantly associated with lifetime-wheeze in both cohorts while maternal smoking during pregnancy was a significant risk factor only in the earlier IoW-cohort. Parental history of rhinitis and grass sensitisation were significantly associated with lifetime-rhinitis in both cohorts while HDM sensitisation was significant only for the IoW-cohort.Conclusion: Contrasting changes were noted with falling wheeze and HDM sensitisation but rising rhinitis and grass sensitisation prevalence. Changing prevalence of aero-allergen sensitisations may explain the different time trends observed in these cohorts

Changing prevalence of wheeze, rhinitis and allergic sensitisation in late childhood:findings from 2 Isle of Wight birth cohorts’ 12-years apart

BACKGROUND: While the prevalence of asthma in children is decreasing or remaining the same, time trends in the prevalence of rhinitis in children are not known. Understanding sensitisation trends may help inform about trends in asthma and rhinitis prevalence.OBJECTIVE: To assess time trends of wheeze, rhinitis and aero-allergen sensitisation prevalence at 10 years of age, we compared two birth cohorts established 12 years apart. To gain insight into differences in disease prevalence, we assessed association of family history, early life exposures and sensitisation with wheeze and rhinitis in each cohort.METHODS: The IoW (Isle of Wight) and FAIR (Food Allergy and Intolerance Research) unselected birth cohorts were established in 1989 and 2001 respectively in IoW. Identical ISAAC questionnaire and skin prick test data were collected and compared at 10 years of age.RESULTS: Over the 12-year period from 2001 to 2012, prevalence of lifetime wheeze, current wheeze and those ever treated for asthma decreased by 15.9% (45.5 vs. 29.6, P &lt; 0.001), 3.9% (18.9 vs. 15, P = 0.020) and 8.2% (31.7 vs. 23.5, P = 0.001), respectively. Conversely, current rhinitis and lifetime rhinitis prevalence increased by 5.5% (22.6 vs. 28.1, P = 0.004) and 13% (18.6 vs. 31.7, P &lt; 0.001), respectively. Atopic status remained stable; however, house dust mite (HDM) sensitisation decreased by 5.6% (19.2 vs. 13.6, P = 0.004) and grass sensitisation increased by 3.5% (12.9 vs. 16.4, P = 0.054). Male sex, parental history of asthma and HDM sensitisation were significantly associated with lifetime wheeze in both cohorts, while maternal smoking during pregnancy was a significant risk factor only in the earlier IoW cohort. Parental history of rhinitis and grass sensitisation was significantly associated with lifetime rhinitis in both cohorts, while HDM sensitisation was significant only for the IoW cohort.CONCLUSION: Contrasting changes were noted with falling wheeze and HDM sensitisation but rising rhinitis and grass sensitisation prevalence. Changing prevalence of aero-allergen sensitisations may explain the different time trends observed in these cohorts

Pathophysiological characterization of asthma transitions across adolescence

BACKGROUND: Adolescence is a period of change, which coincides with disease remission in a significant proportion of subjects with childhood asthma. There is incomplete understanding of the changing characteristics underlying different adolescent asthma transitions. We undertook pathophysiological characterization of transitional adolescent asthma phenotypes in a longitudinal birth cohort.METHODS: The Isle of Wight Birth Cohort (N = 1456) was reviewed at 1, 2, 4, 10 and 18-years. Characterization included questionnaires, skin tests, spirometry, exhaled nitric oxide, bronchial challenge and (in a subset of 100 at 18-years) induced sputum. Asthma groups were "never asthma" (no asthma since birth), "persistent asthma" (asthma at age 10 and 18), "remission asthma" (asthma at age 10 but not at 18) and "adolescent-onset asthma" (asthma at age 18 but not at age 10).RESULTS: Participants whose asthma remitted during adolescence had lower bronchial reactivity (odds ratio (OR) 0.30; CI 0.10 -0.90; p = 0.03) at age 10 plus greater improvement in lung function (forced expiratory flow 25-75% gain: 1.7 L; 1.0-2.9; p = 0.04) compared to persistent asthma by age 18. Male sex (0.3; 0.1-0.7; p &lt; 0.01) and lower acetaminophen use (0.4; 0.2-0.8; p &lt; 0.01) independently favoured asthma remission, when compared to persistent asthma. Asthma remission had a lower total sputum cell count compared to never asthma (31.5 [25-75 centiles] 12.9-40.4) vs. 47.0 (19.5-181.3); p = 0.03). Sputum examination in adolescent-onset asthma showed eosinophilic airway inflammation (3.0%, 0.7-6.6), not seen in persistent asthma (1.0%, 0-3.9), while remission group had the lowest sputum eosinophil count (0.3%, 0-1.4) and lowest eosinophils/neutrophils ratio of 0.0 (Interquartile range: 0.1).CONCLUSION: Asthma remission during adolescence is associated with lower initial BHR and greater gain in small airways function, while adolescent-onset asthma is primarily eosinophilic.</p

Spin and Statistics and First Principles

It was shown in the early Seventies that, in Local Quantum Theory (that is the most general formulation of Quantum Field Theory, if we leave out only the unknown scenario of Quantum Gravity) the notion of Statistics can be grounded solely on the local observable quantities (without assuming neither the commutation relations nor even the existence of unobservable charged field operators); one finds that only the well known (para)statistics of Bose/Fermi type are allowed by the key principle of local commutativity of observables. In this frame it was possible to formulate and prove the Spin and Statistics Theorem purely on the basis of First Principles. In a subsequent stage it has been possible to prove the existence of a unique, canonical algebra of local field operators obeying ordinary Bose/Fermi commutation relations at spacelike separations. In this general guise the Spin - Statistics Theorem applies to Theories (on the four dimensional Minkowski space) where only massive particles with finite mass degeneracy can occur. Here we describe the underlying simple basic ideas, and briefly mention the subsequent generalisations; eventually we comment on the possible validity of the Spin - Statistics Theorem in presence of massless particles, or of violations of locality as expected in Quantum Gravity.Comment: Survey based on a talk given at the Meeting on "Theoretical and experimental aspects of the spin - statistics connection and related symmetries", Trieste, Italy - October 21-25, 200

Tetanus vaccination is associated with differential DNA-methylation: Reduces the risk of asthma in adolescence

BackgroundVaccinations have been suggested to be associated with increased risk of allergic diseases. Tetanus vaccination is one of the most frequently administered vaccines as a part of wound management and was also found to be associated with increased serum IgE levels. We hypothesized that the vaccination modifies the risk of allergic diseases through epigenetic changes such as DNA methylation.MethodData on tetanus vaccination between 10 and 18 years of age was collected from a birth cohort established on the Isle of Wight UK in 1989. DNA methylation data were collected from individuals at different ages (at birth [n = 30], age 10 [n = 34], age 18 [n = 245] and during pregnancy [n = 121]) using the Illumina Infinium HumanMethylation450 K array. Firstly, we performed an epigenome-wide screening to identify cytosine-phosphate-guanine sites (CpGs) associated with tetanus vaccination in 18-year-olds. Secondly, we tested their association with asthma, allergic sensitization, eczema, serum IgE and pulmonary lung function (FVC, FEV1, FEV1/FVC, and FEF25-75%). We then described changes in the methylation of the selected CpG sites over age, and by vaccination status.ResultsTetanus vaccination was found to be associated with decreased methylation of cg14472551 (p value 0.5 × 10?5, FDR-adjusted p value 2.1 × 10?4) and increased methylation of cg01669161 (p value 0.0007, FDR-adjusted p value 0.014). Both CpGs, in turn, were associated with decreased risk of asthma at 18 years of age. Cg14472551 is located in an intron of KIAA1549L, whose protein binds to a B-cell commitment transcription factor; cg01669161 is located between an antisense regulator of the proteasome assembly chaperone PSMG3, and TFAMP1, a pseudogene. Increased methylation of cg01669161 was also associated with decreased serum IgE levels.ConclusionDNA methylation changes following tetanus vaccination may offer a novel prospect to explain a differential occurrence of asthma in adolescence

Sensitization to inhalant allergens between 4 and 8 years of age is a dynamic process: results from the BAMSE birth cohort

Allergic diseases are common in the growing population and have been increasing worldwide. Allergic sensitization, i.e. presence of Immunoglobulin E in the blood, is important for development of allergic disease and sensitization to foods often precedes sensitization to inhalant allergens. Peanut allergy is one of the most prevalent food allergies. It is rarely outgrown and is one of the major causes of fatal and near-fatal allergic reactions. However, asymptomatic peanut sensitization is common, but due to the risk of severe reactions, most peanut sensitized individuals have been regarded as peanut allergic from a clinical point of view. As a consequence, this has resulted in decreased quality of life due to fear of severe reactions. The overall aim of this thesis has been to analyse sensitization patterns to inhalant allergens over time, and to analyse birch pollen- and peanut-IgE antibodies and IgE to peanut allergen components in relation to symptoms of peanut allergy. The study populations in this thesis emanates from A) 4 089 children from a birth cohort (BAMSE) – with follow up at several time points up to eight years of age, Paper I-III and V, and from B) material from a clinical database, established during 2007-2010 of 237 consecutive children with suspected peanut or tree nut allergy, and attending the outpatient allergy clinic at Sachs’ Children’s Hospital. Of these children, 98 were included in study V based on sensitization pattern to peanut allergen components. Paper I describes the dynamic process of sensitization to inhalant allergens. Between four and eight years of age, the proportion of children sensitized to any of the inhalant allergens tested increased from 15% to 25%. At both four and eight years the prevalence of IgE to birch and cat dominated, but sensitization to timothy and dog increased relatively more during this period. In Paper II we showed that children at school age, sensitized both to birch pollen and peanut are less likely to exhibit high IgE levels to peanut and report symptoms to peanut as compared to children with sensitization to peanut, but not to birch pollen. In Paper III IgE reactivity to peanut allergen components in 200 eight-year-old children was investigated. Peanut symptoms were reported in 87% of the children with IgE reactivity to any of the storage proteins of the peanut allergen extract Ara h 1, 2 or 3. This is to be compared with 17% of children with IgE reactivity to Ara h 8 (Bet v 1 homologue), but not to Ara h 1, 2 or 3. Furthermore, symptoms were found to be more severe in children with Ara h 1, 2 or 3 IgE reactivity. Paper IV is a case report from Sachs’ Children’s Hospital, highlighting that sensitization to Ara h 6, homologous to Ara h 2, even in the absence of this latter protein component may cause severe reactions to peanut. This is likely to occur rarely. Paper V supports the suggestion that sensitization to Ara h 8 reflects mild OAS or peanut tolerance at oral peanut challenge. However, sensitization to so far unidentified determinants in peanut may in rare cases cause symptoms. In conclusion, sensitization to inhalant allergens is a dynamic process and birch sensitization dominates at the age of eight. Peanut component Ara h 1-3 sensitization is very often associated with true peanut allergy. Isolated Ara h 8 sensitization seems to indicate peanut tolerance. However, all peanut proteins related to IgE-mediated reactions may not yet have been identified and characterized

Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3–like protein 1

BackgroundDisease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood.ObjectiveWe aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients.MethodsOne hundred ninety-four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy. One hundred three clinical, physiologic, and inflammatory parameters were analyzed by using topological data analysis and Bayesian network analysis.ResultsSevere asthma was associated with anxiety and depression, obesity, sinonasal symptoms, decreased quality of life, and inflammatory changes, including increased sputum chitinase 3–like protein 1 (YKL-40) and matrix metalloproteinase (MMP) 1, 3, 8, and 12 levels. Topological data analysis identified 6 clinicopathobiologic clusters replicated in both geographic cohorts: young, mild paucigranulocytic; older, sinonasal disease; obese, high MMP levels; steroid resistant TH2 mediated, eosinophilic; mixed granulocytic with severe obstruction; and neutrophilic, low periostin levels, severe obstruction. Sputum IL-5 levels were increased in patients with severe particularly eosinophilic forms, whereas IL-13 was suppressed and IL-17 levels did not differ between clusters. Bayesian network analysis separated clinical features from intricately connected inflammatory pathways. YKL-40 levels strongly correlated with neutrophilic asthma and levels of myeloperoxidase, IL-8, IL-6, and IL-6 soluble receptor. MMP1, MMP3, MMP8, and MMP12 levels were associated with severe asthma and were correlated positively with sputum IL-5 levels but negatively with IL-13 levels.ConclusionIn 2 distinct cohorts we have identified and replicated 6 clinicopathobiologic clusters based on blood and induced sputum measures. Our data underline a disconnect between clinical features and underlying inflammation, suggest IL-5 production is relatively steroid insensitive, and highlight the expression of YKL-40 in patients with neutrophilic inflammation and the expression of MMPs in patients with severe asthma