Component-resolved diagnosis in hymenoptera allergy

Component-resolved diagnosis based on the use of well-defined, properly characterised and purified natural and recombinant allergens constitutes a new approach in the diagnosis of venom allergy. Prospective readers may benefit from an up-to-date review on the allergens. The best characterised venom is that of Apis mellifera, whose main allergens are phospholipase A2 (Api m1), hyaluronidase (Api m2) and melittin (Api m4). Additionally, in recent years, new allergens of Vespula vulgaris have been identified and include phospholipase A1 (Ves v1), hyaluronidase (Ves v2) and antigen 5 (Ves v5). Polistes species are becoming an increasing cause of allergy in Europe, although only few allergens have been identified in this venom.In this review, we evaluate the current knowledge about molecular diagnosis in hymenoptera venom allergy.     

THE DUAL EFFECT OF THE PARTICULATE AND ORGANIC COMPONENTS OF DIESEL EXHAUST PARTICLES ON THE ALTERATION OF PULMONARY IMMUNE/INFLAMMATORY RESPONSES AND METABOLIC ENZYMES

ABSTRACT

Exposure to diesel exhaust particles (DEP) is an environmental and occupational health concern. This review examines the cellular actions of the organic and the particulate components of DEP in the development of various lung diseases. Both the organic and the particulate components cause oxidant lung injury. The particulate component is known to induce alveolar epithelial damage, alter thiol levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The organic component, on the other hand, is shown to generate intracellular ROS, leading to a variety of cellular responses including apoptosis. There are a number of differences between the biological actions exerted by these two components. The organic component is responsible for DEP induction of cytochrome P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The particulate component, on the other hand, causes a sustained down-regulation of CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism of xenobiotics and endobiotics remains to be seen, but may prove to be an important factor governing the interplay of the pulmonary metabolic and inflammatory systems. Long-term exposures to various particles including DEP, carbon black (CB), TiO₂, and washed DEP devoid of the organic content, have been shown to produce similar tumorigenic responses in rodents. There is a lack of correlation between tumor development and DEP chemical-derived DNA adduct formation. But the organic component has been shown to generate ROS that produce 8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the particulate, component of DEP suppresses the production of pro-inflammatory cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism for this effect is not yet clear, but may involve the induction of heme oxygenase-1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and the particulate components of DEP enhance respiratory allergic sensitization. Part of the DEP effects may be due to a depletion of glutathione in lymphocytes. The organic component, which is shown to induce IL-4 and IL-10 productions, may skew the immunity toward Th2 response, whereas the particulate component may stimulate both the Th1 and Th2 responses. In conclusion, the literature shows that the particulate and organic components of DEP exhibit different biological actions but both involve the induction of cellular oxidative stress. Together, these effects inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under long-term exposure, induce the development of lung tumors.     

Non-steroidal anti-inflammatory drug hypersensitivity in children

IntroductionThere are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity.MethodsWe conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity.ResultsWe included 119 patients, with a median age of nine years (P₂₅–P₇₅: 5–14). Ibuprofen was the commonest implicated NSAID in the patients’ reports (n = 94–79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n = 95–79.8%), the reaction occurred in the first 24 h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions.ConclusionIn our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis.     

鸡减蛋综合征病毒55K蛋白基因的克隆与序列分析

目的了解鸡减蛋综合征病毒（ＥＤＳＶ）的基因结构特征。方法从中国发病鸡群中分离的鸡减蛋综合征病毒弱毒株ＡＡ２，经常规法提取病毒核酸后，构建了用内切酶ＨｉｎｄⅢ水解的完整基因文库，对其中Ａ片段编码５５Ｋ蛋白基因的核苷酸序列进行测定和分析。结果该读码框共１０１１个核苷酸，编码产物由３３７氨基酸组成，分子量为３８２００。氨基酸同源性分析表明，ＥＤＳＶ５５Ｋ蛋白与人腺病毒（Ａｄ２，Ａｄ１２，Ａｄ４０）、犬腺病毒（ｃａｖ）、Ⅰ群禽腺病毒（ｃｅｌｏ）同源性在２５５％～３２４％之间，而与羊腺病毒（ｏａｖ）的同源性达到４６４％。结论ＥＤＳＶ５５Ｋ蛋白基因具有与腺病毒５５Ｋ蛋白基因相似的结构，但变异较大。     

Early fish introduction is associated with less eczema,but not sensitization,in infants

Objective: To investigate if the development of allergic diseases during the child’s first 18 months of life is influenced by the time at which different food items were introduced into the child’s diet. Method: A birth cohort of 184 children was followed to 18 months of age. Diaries were used to document feeding practices, and parental interviews were performed at 6 and 12 months of age, probing for symptoms suggesting allergic disease, general health‐related issues and food introduction regimes. Symptoms promoted prompt clinical examination, and all children were examined clinically, and tested for sensitization to common airborne and food allergens at 18 months of age. Results: The earlier the fish was introduced into the child’s diet the lower was the frequency of eczema. This association remained after control for confounding factors. The timing of fish introduction and asthma development showed a similar pattern, but did not reach statistical significance. Sensitization was not influenced by the timing of fish introduction. Other food items or feeding practices did not seem to influence allergy development. Conclusion: Early introduction of fish into the child’s diet was associated with less eczema development, and a tendency to less asthma. Sensitization was not associated with the timing of fish introduction.     

Parametric estimation of quality adjusted lifetime (QAL) distribution in progressive illness–death model

In this work, we consider the parametric estimation of quality adjusted lifetime (QAL) distribution in progressive illness–death models. The main idea of this paper is to derive the theoretical distribution of QAL for the progressive illness–death models, under parametric models for the sojourn time distributions in different states, and then replace the model parameters by their estimates obtained by standard techniques of survival analysis. The method of estimation of the model parameters is also described. A data set of IBCSG Trial V has been analyzed for illustration. Extension to more general illness–death models is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Asthma and respiratory infections in school children with special reference to moisture and mold problems in the school

AIM OF THE STUDY: Initially, we performed a questionnaire study on 622 school children aged 7 to 13 y. The study was supplemented with a clinical study including skin prick tests to 13 molds in 212 (34%) children with doctor-diagnosed asthma or parental-reported wheezing or prolonged cough. These children were attending one of two elementary schools, one with moisture problems (index) school, the other being the control school. The objective of the study was to evaluate whether exposure to moisture and sensitization to molds are associated with respiratory manifestations in school children. RESULTS: The prevalence of asthma was 4.8%, which was similar in the children from both schools. The children from the index school more often had wheezing (16% vs 6%; p <0.001) and cough (21% vs 9%: p < 0.001) symptoms than control children. Positive skin reactions to molds were rare (2.4%), being present in 7% of asthmatic and in 1-2% of non-asthmatic children (NS). Lower respiratory tract infections were more common in the spring than in the fall in children from the index school, but not in control children, and the difference between the schools was significant in emergency visits (OR =2.0, p <0.01) and antibiotic courses (OR = 2.1, p < 0.01). CONCLUSIONS: We found evidence of an association between moisture or mold problems in the school building and the occurrence of respiratory infections, repeated wheezing and prolonged cough in school children.     

Stiripentol: efficacy and tolerability in children with epilepsy

PURPOSE: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P450, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed. METHODS: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (108 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial). RESULTS: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p<0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p<0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication. CONCLUSIONS: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.