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

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

MMP-9 gene variants increase the risk for non-atopic asthma in children

<p>Abstract</p> <p>Background</p> <p>Atopic and non-atopic wheezing may be caused by different etiologies: while eosinophils are more important in atopic asthmatic wheezers, neutrophils are predominantly found in BAL samples of young children with wheezing. Both neutrophils as well as eosinophils may secrete matrix metalloproteinase 9 (MMP-9). Considering that MMP-9 plays an important role in airway wall thickening and airway inflammation, it may influence the development of obstructive airway phenotypes in children. In the present study we investigated whether genetic variations in <it>MMP-9 </it>influence the development of different forms of childhood asthma.</p> <p>Methods</p> <p>Genotyping of four HapMap derived tagging SNPs in the <it>MMP-9 </it>gene was performed using MALDI-TOF MS in three cross sectional study populations of German children (age 9-11; N = 4,264) phenotyped for asthma and atopic diseases according to ISAAC standard procedures. Effects of single SNPs and haplotypes were studied using SAS 9.1.3 and Haploview.</p> <p>Results</p> <p>SNP rs2664538 significantly increased the risk for non-atopic wheezing (OR 2.12, 95%CI 1.40-3.21, p < 0.001) and non-atopic asthma (OR 1.66, 95%CI 1.12-2.46, p = 0.011). Furthermore, the minor allele of rs3918241 may be associated with decreased expiratory flow measurements in non-atopic children. No significant effects on the development of atopy or total serum IgE levels were observed.</p> <p>Conclusions</p> <p>Our results have shown that homozygocity for <it>MMP-9 </it>variants increase the risk to develop non-atopic forms of asthma and wheezing, which may be explained by a functional role of MMP-9 in airway remodeling. These results suggest that different wheezing disorders in childhood are affected differently by genetic alterations.</p

Prediction of adult asthma risk in early childhood using novel adult asthma predictive risk scores

Background Numerous risk scores have been developed to predict childhood asthma. However, they may not predict asthma beyond childhood. We aim to create childhood risk scores that predict development and persistence of asthma up to young adult life. Methods The Isle of Wight Birth Cohort (n = 1456) was prospectively assessed up to 26 years of age. Asthma predictive scores were developed based on factors during the first 4 years, using logistic regression and tested for sensitivity, specificity and area under the curve (AUC) for prediction of asthma at (i) 18 and (ii) 26 years, and persistent asthma (PA) (iii) at 10 and 18 years, and (iv) at 10, 18 and 26 years. Models were internally and externally validated. Results Four models were generated for prediction of each asthma outcome. ASthma PredIctive Risk scorE (ASPIRE)-1: a 2-factor model (recurrent wheeze [RW] and positive skin prick test [+SPT] at 4 years) for asthma at 18 years (sensitivity: 0.49, specificity: 0.80, AUC: 0.65). ASPIRE-2: a 3-factor model (RW, +SPT and maternal rhinitis) for asthma at 26 years (sensitivity: 0.60, specificity: 0.79, AUC: 0.73). ASPIRE-3: a 3-factor model (RW, +SPT and eczema at 4 years) for PA-18 (sensitivity: 0.63, specificity: 0.87, AUC: 0.77). ASPIRE-4: a 3-factor model (RW, +SPT at 4 years and recurrent chest infection at 2 years) for PA-26 (sensitivity: 0.68, specificity: 0.87, AUC: 0.80). ASPIRE-1 and ASPIRE-3 scores were replicated externally. Further assessments indicated that ASPIRE-1 can be used in place of ASPIRE-2-4 with same predictive accuracy. Conclusion ASPIRE predicts persistent asthma up to young adult life

Persistent Chlamydia Pneumoniae serology is related to decline in lung function in women but not in men. Effect of persistent Chlamydia pneumoniae infection on lung function

<p>Abstract</p> <p>Background</p> <p><it>Chlamydia pneumoniae </it>(C pn) infection causes an acute inflammation in the respiratory system that may become persistent, but little is known about the long-term respiratory effects of C pn infections. Aim: To estimate the long term respiratory effects of C pn with change in forced expiratory volume in one second (FEV₁) and forced vital capacity (FVC) as a main outcome variable.</p> <p>Methods</p> <p>The study comprised of 1109 subjects (500 men and 609 women, mean age 28 ± 6 years) that participated in the Reykjavik Heart Study of the Young. Spirometry and blood samples for measurements of IgG antibodies for C pn were done at inclusion and at the end of the follow-up period (mean follow-up time 27 ± 4 years).</p> <p>Results</p> <p>Having IgG against C pn at both examinations was significantly associated to a larger decrease in FEV₁(6 mL/year) and FVC (7 mL/year) in women but not in men. In women the association between C pn and larger FEV₁decline was only found in women that smoked at baseline where having C pn IgG was associated with 10 mL/year decline compared to smokers without C pn IgG. These results were still significant after adjustment for age, smoking and change in body weight.</p> <p>Conclusion</p> <p>Our results indicate that persistent C pn serology is related to increased decline in lung function in women but not in men. This effect was, however, primarily found in smoking women. This study is a further indication that the pathophysiological process leading to lung impairment may differ between men and women.</p

Early drug treatment in childhood asthma

Childhood asthma is an increasingly common problem. It is now known that asthma shares similar underlying inflammatory mechanisms to the other major atopic states (rhinitis, atopic dermatitis and food allergy). The notion of an 'allergic march' has been developed to describe the phenomenon by which an atopic individual may exhibit characteristically different atopic states as they grow older. As a result of such knowledge anti-inflammatory strategies have become central to attempts both to prevent as well as to treat asthma during childhood. In some studies children with early atopy such as atopic dermatitis were treated in an attempt to prevent later onset of asthma. It has been proposed that antihistamines might prove effective for this role and in the first part of this review the results of the recently concluded Early Treatment of the Atopic Child study are considered. In the second part, the efficacy and safety of an already widely employed anti-inflammatory strategy, the use of 'early' inhaled corticosteroids for treatment of asthma in children, is examined.</p

Characterisation of atopic and non-atopic wheeze in 10 year old children

Background: Wheezing occurs in both atopic and non-atopic children. The characteristics of atopic and non-atopic wheeze in children at 10 years of age were assessed and attempts made to identify whether different mechanisms underlie these states. Methods: Children were seen at birth and at 1, 2, 4 and 10 years of age in a whole population birth cohort study (n = 1456; 1373 seen at 10 years). Information was collected prospectively on inherited and early life environmental risk factors for wheezing. Skin prick testing, spirometry, and methacholine bronchial challenge were conducted at 10 years. Wheezing at 10 years of age was considered atopic or non-atopic depending on the results of the skin prick test. Independent significant risk factors for atopic and non-atopic wheeze were determined by logistic regression. Results: Atopic (10.9%) and non-atopic (9.7%) wheeze were equally common at 10 years of age. Greater bronchial hyperresponsiveness (p<0.001) and airways obstruction (p = 0.011) occurred in children with atopic wheeze than in those with non-atopic wheeze at 10 years. Children with atopic wheeze more often received treatment (p<0.001) or an asthma diagnosis for their disorder, although current morbidity at 10 years differed little for these states. Maternal asthma and recurrent chest infections at 2 years were independently significant factors for developing non-atopic wheeze. For atopic wheeze, sibling asthma, eczema at 1 year, rhinitis at 4 years, and male sex were independently significant. Conclusions: Non-atopic wheeze is as common as atopic wheeze in children aged 10 years, but treatment is more frequent in those with atopic wheeze. Different risk factor profiles appear relevant to the presence of atopic and non-atopic wheeze at 10 years of age

An unusual bronchial obstruction in a fit young man

We describe the case of a previously well young man who presented acutely to hospital with a history of progressive chest symptoms and systemic upset. At admission, clinical evidence of left upper lobe collapse on respiratory examination and chest x-ray gave rise to significant clinical concern. Initial assessment by CT suggested a possible aspirated foreign body in the left upper lobe bronchus with distal left upper lobe collapse. Subsequent rigid bronchoscopy identified a solid abnormality totally occluding the left upper lobe bronchus, which did not appear to be a foreign body. The patient became progressively more unwell with clinical signs of chest sepsis and failed to settle with medical therapy. A decision was made to undertake a lobectomy to remove the collapsed lobe and obstructing endobronchial lesion. Histology confirmed that the cause of bronchial obstruction was a mesenchymoma (pulmonary hamartoma)