Search

Background House dust mite (HDM) allergens are major elicitors of allergic reactions worldwide. Objective Identification, characterization, and evaluation of diagnostic utility of a new important HDM allergen was performed. Methods A cDNA coding for a new Dermatophagoides pteronyssinus (Dp) allergen, Der p 37, was isolated from a Dp expression library with allergic patients' IgE antibodies. Recombinant Der p 37 (rDer p 37) expressed in Escherichia coli was purified, then characterized by mass spectrometry, circular dichroism, and IgE reactivity by ImmunoCAP ISAC technology with sera from 111 clinically defined HDM-allergic patients. The allergenic activity of rDer p 37 was studied by basophil activation and CD4+ T-cell responses by carboxyfluorescein diacetate succinimidyl ester dilution assays. Specific antibodies raised against rDer p 37 were used for the ultrastructural localization of Der p 37 in mites by immunogold transmission electron microscopy. Results Der p 37, a 26 kDa allergen with homology to chitin-binding proteins, is immunologically distinct from Der p 15, 18, and 23. It is located in the peritrophic membrane of fecal pellets. Der p 37 reacted with IgE antibodies from a third of HDM-allergic patients and induced specific basophil- and CD4+ T-cell activation. Der p 37 IgE–positive patients had significantly higher IgE levels to major HDM allergens, reacted with more HDM allergens, and had a higher risk (odds ratio = 3.1) of asthma compared to Der p 37–negative patients. Conclusions Der p 37, a new Dp allergen recognized by a third of HDM-allergic patients, may serve as a surrogate marker for severe HDM sensitization and asthma.

Vegetables provide important nutrients but can also induce allergic symptoms. Celery tuber allergy frequently occurs in Central European countries and can cause allergic reactions including fatal anaphylactic shocks. There is little information about allergen content in seeds. Therefore, we analyzed 2 patients with allergic reaction after remoulade sauce consumption who entered the clinic for a diagnostic work-up. The routine diagnostic included serum derived specific IgE testing by ImmunoCAP, ImmunoCAP ISAC, and skin prick tests (SPTs). Furthermore, protein extracts were prepared from both celery tuber and celery seeds and IgE binding capacity of these extracts was assessed by immunoblots, ELISA, and rat basophil leukemia (RBL) assay. We also determined role of cross-reactive carbohydrate determinants (CCDs) by IgE inhibition ELISA. Results revealed distinct protein patterns from celery tuber and seed extracts, suggesting differences in content and quantity of allergenic proteins. IgE antibodies from both sera bound to high molecular weight (HMW) proteins on immunoblots and caused high basophil response, which was also observed upon addition of glycosylated proteins as horseradish peroxidase and Api g 5, respectively. Our results indicate that it is worth considering CCDs from plant foods as a possible allergenic factor and their contribution to the mugwort-celery syndrome.

Background: English plantain (Plantago lanceolata) is an important weed pollen allergen source triggering allergic symptoms during summer. To elucidate genuine versus cross-reactive sensitization, we investigated IgE reactivity patterns and inhibition capacities of plantain-sensitized patients. Methods: Sera of 35 rhinoconjunctivitis patients from the north-east of France with positive skin prick tests (SPT) to Plantago lanceolata pollen were tested with clinically relevant allergen sources using ELISA, ImmunoCAP, and immunoblot inhibition. Results: The patients were multisensitized with additional reactivity to grass (94.3%), ash (74.3%), birch (71.4%), and mugwort (55.2%) pollen in SPT. Sensitization prevalence to allergen molecules was 34.3% (Pla l 1), 94.3% (Phl p 1/5), 60.0% (Ole e 1), 65.7% (Bet v 1), 37.1% (profilin), and 40.0% (CCD). In immunoblot, IgE reactivity to plantain pollen was inhibited with relevant pollen extracts and purified rPla l 1. Two sera did not reveal any IgE cross-reactivity, while reactivity to plantain was efficiently inhibited by grass pollen in the sera of 10 patients. The sera from 17 different patients could be inhibited by grass, birch, or ash pollen to varying degrees. Thus, only 37.1% of our patients demonstrated true plantain pollen sensitization, while 62.9% were solely positive due to IgE cross-reactive molecules from other clinically relevant pollen. Conclusions: Plantain pollen-sensitized patients are multi-reactors demonstrating varying and complex IgE-reactivity profiles. In vivo and in vitro tests using extracts are typically blurred due to the presence of homologous allergens or CCD in grass, birch, or ash pollen. So far, Pla l 1 represents the only indicative marker allergen for the diagnosis of genuine plantain pollen sensitization.

English plantain (Plantago lanceolata) is an important weed pollen allergen source triggering allergic symptoms during summer. To elucidate genuine versus cross-reactive sensitization, we investigated IgE reactivity patterns and inhibition capacities of plantain-sensitized patients.Sera of 35 rhinoconjunctivitis patients from the north-east of France with positive skin prick tests (SPT) to Plantago lanceolata pollen were tested with clinically relevant allergen sources using ELISA, ImmunoCAP, and immunoblot inhibition.The patients were multisensitized with additional reactivity to grass (94.3%), ash (74.3%), birch (71.4%), and mugwort (55.2%) pollen in SPT. Sensitization prevalence to allergen molecules was 34.3% (Pla l 1), 94.3% (Phl p 1/5), 60.0% (Ole e 1), 65.7% (Bet v 1), 37.1% (profilin), and 40.0% (CCD). In immunoblot, IgE reactivity to plantain pollen was inhibited with relevant pollen extracts and purified rPla l 1. Two sera did not reveal any IgE cross-reactivity, while reactivity to plantain was efficiently inhibited by grass pollen in the sera of 10 patients. The sera from 17 different patients could be inhibited by grass, birch, or ash pollen to varying degrees. Thus, only 37.1% of our patients demonstrated true plantain pollen sensitization, while 62.9% were solely positive due to IgE cross-reactive molecules from other clinically relevant pollen.Plantain pollen-sensitized patients are multi-reactors demonstrating varying and complex IgE-reactivity profiles. In vivo and in vitro tests using extracts are typically blurred due to the presence of homologous allergens or CCD in grass, birch, or ash pollen. So far, Pla l 1 represents the only indicative marker allergen for the diagnosis of genuine plantain pollen sensitization.

Resume Une mise au point de quatre pollinoses considerees comme rares est presentee. La pollinose au chene, exceptionnelle parmi les pollinoses aux arbres survient a la meme periode que la pollinose aux graminees. L’allergene majeur Que a 1 a une forte homologie avec Bet v 1 et les tests cutanes positifs vis-a-vis du pollen de chene peuvent relever davantage d’une sensibilisation au pollen de bouleau que d’une veritable allergie au pollen de chene. Une etude precise de la saisonnalite des symptomes est fondamentale car les saisons de pollinisation du bouleau et du chene ne se recouvrent que rarement. La pollinose au platane est tres rare en France et les monosensibilisations sont exceptionnelles. Par contre en Espagne, c’est la sensibilisation pollinique la plus frequente, apres les graminees. Elle peut constituer un facteur de risque pour les allergies alimentaires aux vegetaux. L’utilisation des deux allergenes majeurs Pla a 1 et Pla a 2 pour le diagnostic in vitro permet de faire le diagnostic dans 100 % des cas. La pollinose au plantain peut survenir par vagues successives de mars a septembre. Elle est rare en France mais est plus frequente en Angleterre. L’allergene majeur Pla l 1 a des homologies avec l’allergene majeur des oleacees expliquant probablement des co-sensibilisations frequentes. L’allergie au melon et la sensibilisation au pollen de plantain sont souvent associees. La pollinose a l’armoise a une periode de pollinisation specifique dans le Nord et le Sud de la France. C’est la pollinose majeure de l’arriere-saison en Chine. Des co-sensibilisations armoise/ambroisie sont observees. L’allergene majeur est specifique de l’armoise mais d’autres allergenes du pollen d’armoise peuvent etre responsables d’allergie croisee avec l’ambroisie en particulier Art v 6, une pectatelyase. Les allergies croisees alimentaires sont nombreuses et complexes et leurs rapports moleculaires sont de mieux en mieux identifies. Outre les donnees de la litterature, une etude retrospective de 273 bilans cutanes allergologiques est presentee : elle souligne la rarete de la sensibilisation vis-a-vis de ces pollens et la frequence des co-sensibilisations vis-a-vis d’autres pollens.

Resume Objectif de l’etude Le but de l’etude est de determiner la valeur ajoutee de l’etude du profil de sensibilisation moleculaire chez les patients allergiques au poisson. Patients et methodes Le diagnostic d’une allergie au poisson a ete retenu chez 62 patients sur la base d’une histoire clinique evocatrice, de tests cutanes et d’IgE specifiques positives aux extraits de poisson (cabillaud, saumon, thon). La determination des IgE specifiques vis-a-vis de la parvalbumine, de l’enolase, de l’aldolase et de la gelatine de poisson, quantifiees par Elisa, a ete realisee chez tous les patients. Resultats Quarante-cinq patients sont sensibilises a la parvalbumine. Chez les patients sensibilises a la parvalbumine de cabillaud (morue), 50 % sont egalement sensibilises a l’enolase et a l’aldolase. Chez les patients ayant des tests cutanes positifs au saumon et au thon (75,6 % et 67,6 % respectivement), des sensibilisations isolees a la parvalbumine ont ete observees. Une correlation positive est observee entre les taux moyens des IgE specifiques envers la parvalbumine et l’enolase de cabillaud, et la severite du tableau clinique, ce qui n’est pas le cas pour l’aldolase de cabillaud. Trois groupes de patients ont ete analyses selon leur degre de reactivite IgE envers la parvalbumine : un premier groupe ( n = 36) compose de patients sensibilises aux 3 poissons avec des symptomes moderes a severes. Les symptomes sont correles a la presence d’IgE au cabillaud (extrait total) et a la parvalbumine de cabillaud. Un second groupe est constitue de patients ( n = 9) monosensibilises et ayant une allergie de gravite mineure, principalement au saumon. Les symptomes sont correles a des IgE specifiques envers l’extrait de saumon et envers la parvalbumine de saumon. Le troisieme groupe est compose de patients ( n = 17) sensibilises a un nombre restreint de poissons et presentant des symptomes moderes a severes. Chez ces patients dont les IgE etaient negatives envers la parvalbumine, on objective la presence d’IgE a l’aldolase, l’enolase ou a la gelatine de poisson dans 70,6 % des cas. Danc ce dernier groupe, la presence d’IgE specifiques envers le cabillaud est rarement observee. Conclusion L’utilisation d’un panel d’allergenes moleculaires de poisson varies contribue a l’amelioration du diagnostic de l’allergie au poisson. Certains profils de sensibilisation semblent associes a des tableaux cliniques particuliers.

Resume La taxonomie, la morphologie, le cycle biologique des acariens Pyroglyphides (dont font partie les Dermatophagoides) et des acariens de stockage (Acaridae, Glycyphagidae et Blomia tropicalis ) sont rappeles. Leur anatomie est tres voisine mais la fecondite des acariens de stockage est plus importante. L’humidite relative est le parametre essentiel qui regule leur proliferation. La literie est la niche ecologique privilegiee des Pyroglyphides qui se nourrissent de squames humaines ; les acariens de stockage se nourrissent de denrees alimentaires et ne sont pas exclusivement retrouves dans le secteur agricole. Dans les regions tropicales Blomia tropicalis est un acarien de la poussiere de maison. Depuis 1988 les connaissances moleculaires des allergenes des acariens se sont considerablement enrichies, leurs structures et leurs fonctions ont pu etre precisees pour la majorite d’entre eux. 23 allergenes ont ete identifies. Les groupes 1 et 2 ont une homologie de sequence en AA de 85 % et sont des allergenes majeurs. Les groupes 4, 5, 7, 11, 14,15, 23 sont egalement des groupes importants. La liaison aux IgE des groupes 3, 8, 10, 20 est faible. Nombre d’allergenes ont une fonction biochimique : cysteine proteases pour les allergenes du groupe 1, amylases, serine proteases par exemple. Der p 2 a une homologie de structure et de fonction avec MD-2, co-recepteur du recepteur TLR4, dont les LPS sont le ligand. Des reactions croisees ont ete mises en evidence : majeures au sein d’une meme famille, plus faibles entre allergenes de familles differentes. Les applications pratiques sont soulignees : explications des cosensibilisations, interet de l’epidemiologie moleculaire, permettant le choix des allergenes a utiliser pour le diagnostic, enfin utilisation future dans les desensibilisations specifiques.

Background: The results of international epidemiological surveys show large geographical variations in skin test reactivity but do not provide a rationale for such variations. Objective: To assess the relationship between climate and allergic sensitization in schoolchildren. Methods: In the present study, we analyzed data from a multicenter, epidemiological survey that included 6,461 schoolchildren, aged 9-11 years, living in 6 French cities scattered around France. The protocol also included a battery of skin prick tests to common airborne allergens. The crude prevalence of sensitization to each allergen was estimated for each city and then adjusted for potential confounding factors. This analysis was repeated for monosensitization and for allergens grouped into 2 categories: indoor allergens, i.e., house dust mite (HDM), cat, and cockroach allergens, and outdoor allergens, i.e., birch pollen, grass pollen, and Alternaria. We also grouped cities according to their location on the coast, i.e., Marseille and Bordeaux, or inland, i.e., Créteil, Clermont-Ferrand, Reims, and Strasbourg. Results: A difference in prevalence of sensitization to each airborne allergen or allergens grouped into indoor and outdoor categories was found between cities, even after adjusting for potential confounding factors. Also, a higher prevalence of sensitization to HDM, cat dander, and, broadly speaking, indoor allergens, was found in children living on the coast than in those living inland, whereas they showed a lower prevalence of sensitization to birch pollen. Between-city differences in the prevalence of monosensitization were also statistically significant. Children living in coastal cities had a higher rate of monosensitization to indoor allergens and a lower prevalence of sensitization to birch pollen. The higher prevalence of allergic sensitization in children from coastal cities is most likely due to climatic conditions, such as proximity from sea and humidity. Differences in sensitization to birch allergens could be due to differential exposure to these pollen. Conclusion: These results indicate a role of environmental exposure in sensitization to perennial as well as seasonal allergens.

The availability of allergen molecules ('components') from several protein families has advanced our understanding of immunoglobulin E (IgE)-mediated responses and enabled 'component-resolved diagnosis' (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low-abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross-reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE-mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross-reactive panallergens from plant (lipid transfer proteins, polcalcins, PR-10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE-mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.

Resume La taxonomie, la morphologie, le cycle biologique et l’ecologie des acariens pyroglyphides et des acariens de stockage sont compares. L’anatomie des acariens pyroglyphides et des acariens de stockage est voisine, il existe cependant des clefs qui permettent de les differencier comme la presence de poils sensoriels chez les glycyphagidae ou d’un appareil urinaire chez les acaridae. La fecondite des acariens de stockage est nettement superieure a celle des pyroglyphides. L’humidite relative et la temperature optimales sont de 80 % et de 30 °C pour les acariens de stockage qui se nourrissent de denrees alimentaires et de moisissures. Initialement consideres comme des acariens du secteur agricole et des professions qui s’y rattachent, les acariens de stockage sont egalement des acariens du milieu urbain humide. Les symptomes entraines par les acariens de stockage sont respiratoires, mais aussi dermatologiques et anaphylactiques. Les allergenes majeurs font partie du groupe 2 ; entre allergenes du groupe 2 les relations sont etroites et les reactivites croisees importantes, alors qu’avec les allergenes des acariens pyroglyphides les reactivites croisees sont faibles.

BACKGROUND: Cow's milk is one of the most common causes of food allergy. In two-thirds of patients, adverse symptoms following milk ingestion are caused by IgE-mediated allergic reactions, whereas for one-third, the mechanisms are unknown. Aim of this study was to investigate whether patients suffering from non-IgE-mediated cow's milk protein intolerance can be distinguished from persons without cow's milk protein intolerance based on serological measurement of IgG and IgA specific for purified cow's milk antigens. METHODS: We determined IgG(1-4) subclass and IgA antibody levels to purified recombinant ?S1-casein, ?S2-casein, ?-casein, ?-casein, ?-lactalbumin, and ?-lactoglobulin in four patient groups by ELISA: Patients with IgE-mediated cow's milk allergy (CMA, n=25), patients with non-IgE-mediated cow's milk protein intolerance (CMPI, n=19), patients with gastrointestinal symptoms not associated with cow's milk ingestion (GI, n=15) and control persons without gastrointestinal problems (C, n=26). Cow's milk-specific IgE levels were determined by ImmunoCAP. RESULTS: Only CMA patients had IgE antibodies to cow's milk. Cow's milk allergic patients mounted the highest IgG(1) and IgG(4) antibody levels to ?S1-casein, ?S2-casein, ?-casein, ?-casein, and ?-lactalbumin. No elevated levels of IgG(4) , IgA, and complement-binding IgG subclasses (IgG(1) , IgG(2) , IgG(3) ) to purified cow's milk allergens were found within the CMPI patients compared to persons without cow's milk protein intolerance (GI and C groups). CONCLUSION: Cow's milk protein intolerant patients cannot be distinguished from persons without cow's milk protein intolerance on the basis of IgG subclass or IgA reactivity to cow's milk allergens.

Purpose of review Subcutaneous immunotherapy is a well documented treatment of allergic rhinitis and asthma. The majority of the disadvantages of the treatment are related to the poor quality of the natural allergen extracts which can contain varying amounts of individual allergens including allergens to which the patient may not be sensitized. Recombinant allergens offer a possibility to use well defined molecules with consistent pharmaceutical quality defined in mass units. The proof of concept of the clinical efficacy of recombinant allergens is based on two studies published as full articles. Recent findings One study applied a mixture of five Phleum pratense major allergens in a maximum dose of 40mcg protein. The clinical efficacy showed a significant efficacy with 40% reduction in disease severity. The second study compared a commercial birch extract with both recombinant Bet v 1 and purified Bet v 1 in dosages of 15mcg allergen. The clinical effect was 60% additional efficacy. Systemic side effects occurred more frequently with grass allergens. A third study used hypoallergenic fragments and a trimer of Bet v 1. The study did not show efficacy and a rather high frequency of systemic side effects. Summary The advantages of using recombinant allergens for immunotherapy are obvious but more studies on a large scale are needed before the overall value in terms of efficacy and safety can be assessed. Clinical trials are also necessary for new combined vaccines based on recombinant allergens that in experimental studies have shown greatly enhanced immunogenicity and low allergen-specific reactivity.

SummaryBackground Cow’s milk is one of the most common causes of food allergy affectingapproximately 2.5% of infants in the first years of their life. However, only limitedinformation regarding the allergenic activity of individual cow’s milk allergens is available.ObjectiveToanalysethefrequencyofIgEreactivityandtodeterminetheallergenicactivityofindividual cow’s milk allergens.MethodsA nitrocellulose-based microarray, based on purified natural and recombinant cow’smilk allergens was used to determine IgE reactivity profiles using sera from 78 cow’s milk-sensitized individuals of varying ages. The allergenic activity of the individual allergens wastested using patients’ sera for loading rat basophil leukaemia cells (RBL) expressing thea-chain of the human receptor FceRI.Results Using the microarray and the RBL assay, cow’s milk allergens were assessed forfrequency of IgE recognition and allergenic activity. Moreover, the RBL assay alloweddistinguishing individuals without or with mild clinical reactions from those with severesystemic or gastrointestinal symptoms as well as persons who grew out cow’s milk allergyfrom those who did not.Conclusions Component-resolved testing using milk allergen microarrays and RBL assaysseems to provide useful additional diagnostic information and may represent a basis forfuture forms of prophylactic and therapeutic strategies for cow’s milk allergy.Keywords Basophil degranulation, cow’s milk allergy, diagnosis, microarray, recombinantallergenSubmitted 15 March 2010; revised 8 June 2010; accepted 13 July 2010

Methodes Trente-cinq serums d’enfants asthmatiques gabonais ont ete analyses pour determiner les sensibilisations aux allergenes moleculaires de B. tropicalis (Bt) et des dermatophagoides (DP). Les dosages ont ete effectues par dot-blot pour 7 allergenes moleculaires de Bt (Blo t 2, Blo t 5, Blo t 8, Blo t 10, Blo t 12, Blo t 13, Blo t 21) et par la biopuce-ImmunoCAP ISAC (MedAll) pour 17 allergenes des acariens (Blo t 5, Lep d 2, Der p 1, Der f 1, Der p 2, Der f 2, Der p 4, Der p 5, Der p 7, Der p 10, Der p 11, Der p 14, Der p 15, Der p 18, Der p 21, Der p 23). Taux exprimes en ISU (cut-off : 0,1 ISU). Resultats Des IgE specifiques pour des allergenes moleculaires de Bt et/ou des DP sont mis en evidence dans 69 % des cas. Les sensibilisations a Bt montrent des taux eleves d’IgE anti-Blo t 5 (med : 61,85 ISU), correles aux resultats des dot-blots. L’association des positivites des IgE pour les 2 allergenes majeurs Blo t 5 et Blo t 21 est constante. Dans 3 cas une monosensibilisation a Blo t 2 est mise en evidence, associee dans 2 cas sur 3 a des taux eleves d’IgE vis-a-vis des allergenes du groupe 2 des DP, suggerant une reactivite croisee. Les cosensibilisations aux allergenes des acariens DP sont observes a des taux significatifs vis-a-vis de Der p 1, Der p 2, Der p 23 (5 cas), pour Der p 5, Der p 7, Der 21 (4 cas), pour des allergenes majeurs et intermediaires (3 cas). L’etude des cosensibilisations de Blo t 5 avec des allergenes des DP, ayant des homologies de sequences avec ceux de Bt, montrent une association a Der p 5 (9/14), et une association a Der p 21 (11/14) ; les taux d’IgE anti-Blo t 5 sont plus toujours plus eleves que les taux d’IgE anti-Der p 5 et anti-Der p 21. Dans 2 cas il existe une sensibilisation exclusive aux allergenes du groupe 2 des DP. Conclusion Bien qu’une cosensibilisation aux 2 especes d’acariens soit la situation la plus frequente, les taux eleves d’IgE anti-Blo t 5 et l’association constante d’une sensibilisation aux 2 allergenes majeurs de Bt sont en faveur du role majeur de cet acarien en Afrique equatoriale. L’association a des IgE vis-a-vis d’allergenes potentiellement croisants est frequente mais leur taux est plutot en faveur du role primosensibilisant de Bt.

The present document is a consensus statement reached by a panel of experts on noninvasive methods for assessment of airway inflammation in the investigation of occupational respiratory diseases, such as occupational rhinitis, occupational asthma, and nonasthmatic eosinophilic bronchitis. Both the upper and the lower airway inflammation have been reviewed and appraised reinforcing the concept of 'united airway disease' in the occupational settings. The most widely used noninvasive methods to assess bronchial inflammation are covered: induced sputum, fractional exhaled nitric oxide (FeNO) concentration, and exhaled breath condensate. Nasal inflammation may be assessed by noninvasive approaches such as nasal cytology and nasal lavage, which provide information on different aspects of inflammatory processes (cellular vs mediators). Key messages and suggestions on the use of noninvasive methods for assessment of airway inflammation in the investigation and diagnosis of occupational airway diseases are issued.

Resume Pour preciser le role des particules fines dans le developpement des maladies allergiques de l’enfant, nous avons realise une etude epidemiologique transversale chez des enfants scolarises en primaire dans six villes francaises. Nous avons mesure durant une semaine le taux de particules fines (PM2,5) et de dioxyde d’azote (NO2) sous les preaux des ecoles et recueilli les mesures effectuees par les reseaux urbains de surveillance de la qualite de l’air. Lors de l’examen medical a l’ecole, les enqueteurs notaient la presence d’une dermatite atopique et faisaient realiser un test de course pour evaluer l’existence d’une eventuelle hyperreactivite bronchique. Par ailleurs, le questionnaire parental evaluait les antecedents personnels et familiaux de l’enfant, les symptomes respiratoires et l’environnement domestique. Au total, 5338 enfants d’âge moyen (plus ou moins ecart-type) 10,4 plus ou moins 0,7 ans, provenant de 108 ecoles et 401 classes ont participe a l’enquete. L’exposition aux PM2,5 et au NO2 a ete classee de maniere dichotomique par rapport a la mediane des mesures. Les analyses de regression logistique, apres ajustement sur les variables de confusion potentielles, ont mis en evidence un risque statistiquement significatif de dermatite atopique, d’hyperreactivite bronchique lors du test de course, d’antecedents d’asthme allergique et de sensibilisation vis-a-vis des allergenes domestiques chez les enfants du groupe plus expose aux PM2,5 a proximite de leur habitation. Ces resultats plaident en faveur du role causal de ces particules dans le developpent de l’atopie, de l’hyperreactivite bronchique et de l’asthme.

Background House dust mites (HDM) Dermatophagoides pteronyssinus are a frequent indoor allergen source. Our aim was to determine the frequencies of IgE reactivity to purified HDM allergen molecules in mite allergic patients from different parts of Europe in order to establish an allergen panel for diagnosis of HDM allergy. Materials and methods Populations of D. pteronyssinus-allergic patients from Austria (n = 56), France (n = 55), Italy (n = 67) and Sweden (n = 65) and storage mite allergic patients from Sweden (n = 31) were analysed for IgE reactivity to eight purified natural (n) and recombinant (r) D. pteronyssinus allergens (nDer p 1, rDer p 2, nDer p 4, rDer p 5, rDer p 7, rDer p 8, rDer p 10 and rDer p 14) in RAST-based dot blot assays. Results Using a combination of Der p 1 and Der p 2, at least 97% of the D. pteronyssinus-allergic patients could be diagnosed in each of the HDM allergic populations. However, more than 50% of the patients also reacted with other allergens and significant variabilities regarding the frequencies of IgE reactivity to individual allergen molecules were found. Patients with a predominant storage mite allergy showed none or only very weak IgE reactivity to purified D. pteronyssinus allergens. Conclusions Purified Der p 1 and Der p 2 are sufficient for the diagnosis of ≥ 97% of D. pteronyssinus allergic patients in Europe, but other allergens may also play an important role for the diagnosis and treatment of HDM allergy.

Recombinant DNA technology has the potential to produce allergen-specific immunotherapy vaccines with defined composition.To evaluate the effectiveness of a new recombinant birch pollen allergen vaccine in patients with birch pollen allergy.A multicenter, randomized, double-blind, placebo-controlled trial was undertaken to compare the following 3 vaccines in 134 adults with birch pollen allergy: recombinant birch pollen allergen vaccine (rBet v 1a), licensed birch pollen extract, natural purified birch pollen allergen (nBet v 1), and placebo. Patients received 12 weekly injections followed by monthly injections of the maintenance dose containing 15 microg Bet v 1 for 2 years.Significant reductions (about 50%) in rhinoconjunctivitis symptoms (rBet v 1, P = .0002; nBet v 1, P = .0006; birch extract, P = .0024), rescue medication (rBet v 1, P = .0011; nBet v 1, P = .0025; birch extract, P = .0063), and skin sensitivities (P.0001) were observed in the 3 actively treated groups compared with placebo during 2 consecutive pollen seasons. Clinical improvement was accompanied by marked increases in Bet v 1-specific IgG levels, which were higher in the rBet v 1-treated group than in the birch and nBet v 1-treated groups. New IgE specificities were induced in 3 of 29 patients treated with birch pollen extract, but in none of the 32 rBet v 1-treated or 29 nBet v 1-treated patients. No severe systemic adverse events were observed in the rBet v 1-treated group.The rBet v 1-based vaccine was safe and effective in treating birch pollen allergy, and induced a highly specific immune response.

Introduction L’asthme professionnel avec periode de latence induite apres des expositions repetees, se caracterise par une sensibilisation immunologique a l’agent responsable pouvant etre IgE- dependante, et une hyperreactivite bronchique non specifique. Methodes diagnostiques L’interrogatoire est un element capital des investigations de l’asthme professionnel. Les elements evocateurs sont la survenue de symptomes en periode de travail et l’amelioration durant les conges. Ce dernier facteur a le meilleur niveau de preuve (grade 2+) lors de l’analyse de plusieurs publications selon les criteres de medecine bases sur les preuves. L’etude du poste de travail est fondamentale, basee sur la cooperation avec le medecin du travail. Des resultats positifs du bilan immunologique (tests cutanes et/ou recherche d’IgE specifiques) associes a des criteres objectifs de symptomes en relation avec le travail (modification du DEP, des EFR et/ou de l’HRBNS) permettent de preciser le diagnostic etiologique de l’asthme professionnel. Les tests de provocation bronchique specifique necessitant des equipes entrainees, apportent la preuve de la responsabilite de nouvelles substances et sont un recours necessaire lorsque les autres investigations ne sont pas disponibles ou sont discordantes. L’asthme professionnel necessite une demarche par etapes successives dans lesquelles peuvent egalement s’integrer la recherche d’eosinophiles dans l’expectoration et la mesure du NO exhale. Prise en charge L’asthme professionnel necessite une eviction du milieu du travail car la persistance de l’exposition peut entrainer une aggravation progressive de l’asthme et sa perennisation. Cependant, l’eviction professionnelle a souvent des consequences sociales et financieres deleteres, ce qui peut autoriser d’envisager un compromis avec une reduction de l’exposition par differents amenagements accompagnes d’un traitement adapte. Le traitement de l’asthme professionnel ne differe pas de celui de l’asthme en general, il doit etre ajuste selon les criteres de gravite en utilisant bronchodilatateurs et corticoides. Sur le plan medico-legal, l’asthme professionnel peut etre reconnu apres declaration en maladie professionnelle. En France, l’asthme est mentionne dans plusieurs tableaux de maladie professionnelle.

Summary Background Birch pollen and pollen from related trees of the Fagales order are a major cause of allergic rhinitis, conjunctivitis, and asthma through the spring season in northern and central Europe. Objective To investigate the clinical effects of injection immunotherapy with genetically modified derivatives of major birch pollen allergen Bet v 1 on pollen-induced allergic symptoms. Methods A three-arm double-blind placebo-controlled immunotherapy study was conducted with one pre-seasonal course of treatment using two derivatives of Bet v 1, namely a recombinant Bet v 1 trimer and an equimolar mixture of two recombinant Bet v 1 fragments together representing the whole protein sequence. Analysis of local and systemic adverse events was performed for 124 patients who had received at least one dose of medication. Clinical efficacy was monitored by symptom medication scores and interval scoring in the per protocol-treated population (n=84). In addition, skin and nasal provocation responses and allergen-specific antibodies were assessed. Results There were trends towards improvement in the subjects' well-being and clinical symptoms (nasal scores), although comparisons with a placebo group did not show statistical significance in the main end-point, the combined symptom medication score. Reductions in skin and nasal sensitivity were observed for some subjects with a trend for the Bet v 1 trimer to be more effective than the fragments. Treatment induced strong IgG1 and IgG4 allergen-specific antibody responses. Local injection-site reactions were most frequent in the trimer group affecting 59.5% of patients as opposed to 37.8% and 30.6% in the fragment and placebo groups, respectively. Systemic reactions were elicited more frequently by fragments. A large proportion of adverse side-effects appeared hours following injections, and might be attributable to concurrent exposure to related pollens. Conclusion Single courses of injection immunotherapy with Bet v 1 allergen derivatives showed trends towards improved well-being and reduced reactivity to specific allergen provocation, but did not yield significant improvement in the combined symptom medication score in this study.

Introduction L’Observatoire National des Asthmes Professionnels est un systeme de signalement volontaire instaure en France en 1996 pour preciser l’incidence de cette pathologie et ses caracteristiques. Materiel et methodes En utilisant la meme procedure de recueil et de traitement des signalements d’asthme professionnel que celle utilisee au niveau national depuis 1996, nous avons realise une inclusion plus large des medecins, sollicite plus frequemment leur participation et majore la frequence des informations en Alsace en 2001 et 2002. L’objectif de l’etude est de suivre les repercussions de cette procedure sur le nombre de cas recenses, le but etant d’ameliorer l’exhaustivite des donnees. Resultats L’incidence de l’asthme professionnel (AP) est ainsi estimee a 126 cas/million de travailleurs. Une predominance feminine des cas d’asthme professionnel est observee pendant la periode 2001-2002 (52,4 %), ce qui n’etait pas le cas auparavant. L’etude des etiologies met en evidence, comme cela a ete observe au niveau national, deux categories predominantes, regroupant 40 % des asthmes signales : les farines et les isocyanates. Les persulfates representent 5,3 % des cas signales, le latex et les aldehydes 2,6 %, respectivement. Il existe des particularites regionales avec notamment un taux eleve d’asthme aux isocyanates (21,1 %) et des signalements d’etiologies moins habituelles telles que les ammoniums quaternaires. Conclusion Le renforcement des moyens en Alsace a permis d’ameliorer sensiblement le recueil des cas incidents d’AP et de degager des particularites regionales qui incitent au maintien de ce systeme de surveillance.

Allergen extracts have been used for diagnosis and treatment of allergy for around 100 years. During the second half of 20th century, the notion increasingly gained foothold that accurate standardization of such extracts is of great importance for improvement of their quality. As a consequence, manufacturers have implemented extensive protocols for standardization and quality control. These protocols have overall IgE-binding potencies as their focus. Unfortunately, each company is using their own in-house reference materials and their own unique units to express potencies. This does not facilitate comparison of different products. During the last decades, most major allergens of relevant allergen sources have been identified and it has been established that effective immunotherapy requires certain minimum quantities of these allergens to be present in the administered maintenance dose. Therefore, the idea developed to introduce major allergens measurements into standardization protocols. Such protocols based on mass units of major allergen, quantify the active ingredients of the treatment and will at the same time allow comparison of competitor products. In 2001, an EU funded project, the CREATE project, was started to support introduction of major allergen based standardization. The aim of the project was to evaluate the use of recombinant allergens as reference materials and of ELISA assays for major allergen measurements. This paper gives an overview of the achievements of the CREATE project.

Resume Les anomalies de l’hemostase sont retrouvees chez pres de 90 % des patients atteints de cancer, mais n’ont d’expression clinique que dans 15 % des cas environ. Les complications hemorragiques sont plus frequentes lors des leucemies aigues, tandis que les accidents thromboemboliques sont plus volontiers retrouves dans les tumeurs solides. La coagulation intravasculaire disseminee (CIVD) est un syndrome de presentation latente ou aigue, qui survient dans l’evolution de diverses affections graves, notamment neoplasiques, et s’accompagne d’une augmentation de la morbidite et de la mortalite. Quelle qu’en soit l’etiologie, les CIVD se manifestent par des tableaux tres varies, allant de minimes alterations biologiques de la coagulation, aux microthromboses intravasculaires et extravasculaires, voire aux manifestations hemorragiques fatales. Nous rapportons l’observation d’une patiente de 45 ans presentant un adenocarcinome bronchique metastatique au moment du diagnostic, chez laquelle sont survenues de nombreuses complications thromboemboliques dans le cadre d’une CIVD, ayant entraine son deces. Cette observation permet d’exposer certaines complications peu frequentes de la CIVD et de discuter l’objectif therapeutique principal qui est de moduler la generation demesuree de thrombine, responsable de thromboses et/ou d’hemorragies par consommation des facteurs cellulaires et plasmatiques de la coagulation, par un traitement symptomatique et surtout etiologique (donc chimiotherapeutique), lui-meme susceptible a son tour de favoriser les complications thromboemboliques.

Quaternary Ammonium Compounds (QACs) are widely found in disinfectants used in hospitals. Benzalkonium chloride (BAC) and didecyldimethylammonium chloride (DDAC) predominate in the disinfecting formulations. These compounds are strong irritants and can play a role in the induction of Occupational Asthma among the professionals of health and cleaning. In order to evaluate the potential health effect of these quaternary ammonium compounds to hospital employers, the development of an analytical method for their quantification in indoor air was developed. DDAC aerosols are trapped by adsorption on XAD-2 resin SKC tube. The air in hospital buildings was sampled using a constant debit Gillian pump at a flow of 1.0 l/min (+/-5%). Ion Chromatography (IC) was chosen for the analysis of DDAC especially for its high sensitivity and specificity. The Limit of Detection (LOD) by IC for DDAC is 0.56 mug/ml. Therefore the LOD of atmospheric DDAC is 28 microg/m(3) with an air volume of 100 l and a desorption volume of 5 ml. All DDAC air samples were lower than the LOD of the analytical method by IC. Under the standard conditions of use of the disinfecting solutions (Surfanios, Ampholysine Plus and Amphospray 41), the insignificant volatility of DDAC would not seem to be able to contaminate the indoor hospital atmosphere during the disinfection process. However, the DDAC can contaminate working atmospheres if it is put in suspension by aerosolisation.

Background: Ash tree (Fraxinus excelsior) is the main representative of the Oleaceae family in temperate zones. Diagnosis of ash pollen allergy is made difficult due to (1) an overlapping pollinization period with Betulaceae, (2) non-inclusion in current diagnostic assays, and (3) some cross- reactivity with minor allergens from Betulaceae. The aim of this study was to calibrate an ash pollen in-house reference preparation (IHRP) in allergic patients in order to produce standardized products for diagnosis and immunotherapy purposes. Methods: Ash pollen IHRP was extracted, ultrafiltered and freeze dried. Allergens in the extract were detected after 2-dimensional PAGE using specific sera and a monoclonal antibody. The Fra e 1 content of IHRP was evaluated by quantitative immunoprint. Forty-eight subjects from the North-East of France exhibiting clinical symptoms, a positive skin test and specific IgE levels ≧class 2 to ash pollen were recruited. IgE immunoprints were performed to select patients sensitized to the ash Fra e 1 allergen as opposed to cross-reacting allergens. Serial 10-fold dilutions of the IHRP were tested by skin prick tests in order to determine the concentration inducing a geometrical mean wheal diameter of 7 mm, said to correspond to an index of reactivity (IR) of 100 per millilitre. Results: IgE-reactive molecules in IHRP comprise Fra e 1, Fra e 2, a 9-kDa molecule (presumably Fra e 3), as well as a doublet at 15 kDa and high molecular weight allergens. The 100 IR concentration of IHRP inducing a geometrical mean wheal diameter of 7 mm in 22 patients sensitized to Fra e 1 corresponds to the 1/126 (w/v) extraction ratio (i.e. 259 µg/ml of protein by Bradford) and contains 17 µg/ml of Fra e 1. The variability in total activity of 5 batches of standardized extracts was found to be significantly reduced when compared with 7 non-standardized extracts. Conclusion: An ash pollen IHRP was defined and molecularly characterized. Its successful standardization at 100 IR/ml in patients specifically sensitized to Fra e 1 allowed a skin reactivity-based calibration in properly diagnosed patients. Such a standardized ash pollen extract is a reliable tool to support immunotherapy of ash pollen allergy.

Resume Les metastases hypophysaires sont rares et peu symptomatiques. Nous rapportons ici les observations de 5 patients ayant une metastase hypophysaire de cancer bronchique permettant d’illustrer les differents modes de decouverte. Ces metastases ont ete, dans tous les cas, symptomatiques, et leur principale manifestation a ete le diabete insipide, puis les troubles du champ visuel. Les cancers bronchiques chez nos 5 patients sont aussi bien a petites cellules que non a petites cellules. Le pronostic apres le diagnostic de metastase hypophysaire est sombre mais semble plutot lie a l’histologie et au stade du cancer bronchique qu’a l’extension a cette localisation particuliere.

Resume Les differents outils diagnostiques allergologiques auxquels peuvent faire appel les cliniciens sont obtenus a partir d'extraits allergeniques globaux. Ces extraits contiennent plusieurs proteines allergeniques et leur composition peut etre variable. L'application de la biologie moleculaire aux allergenes a permis d'obtenir des allergenes recombinants de differentes sources allergeniques. L'utilisation de ces derniers a permis d'ameliorer la connaissance des proteines allergeniques, de definir des familles d'allergenes, de donner les bases des allergies croisees et de definir des profils de sensibilisation pollinique individuels pouvant varier en fonction des zones geographiques. De ce fait, le raisonnement a l'echelle moleculaire devrait, au XXIe siecle, etre integre a la prise en charge du patient. En 2005, le clinicien dispose du dosage d'IgE specifiques de 27 allergenes recombinants issus de sept sources allergeniques differentes. Leur utilisation peut, dans certains cas, permettre d'etablir un diagnostic plus efficace et de mieux orienter les choix therapeutiques. Trois observations issues de notre consultation sont rapportees afin d'illustrer l'apport de ces nouvelles techniques diagnostiques.

Resume Une ouvriere de 39 ans chargee de la fabrication des saucisses dans une charcuterie industrielle a decrit de l'urticaire puis une rhinite et un asthme apres sept ans d'exposition avec des boyaux de porc ou de leur liquide de rehydratation (LR). L'ingestion de viande de porc est a l'origine d'une crise d'asthme. Cette patiente atopique (sensibilisation aux allergenes de chat et de chien et possedant un chat au domicile) a des prick-tests positifs pour l'albumine de porc, les gammaglobulines de porc et de chat, le LR des boyaux de porc. Les IgE specifiques sont positives pour les albumines (chat, porc, bœuf) ; la viande de porc, bœuf, mouton ; les boyaux de porc et le LR. Le diagnostic d'asthme est confirme par un test de provocation bronchique specifique positif avec le LR (chute de 23 % du VEMS en immediat). L'immunoblot du LR et l'inhibition du blot mettent en evidence des IgE seriques dirigees vis-a-vis de l'albumine et des gammaglobulines de porc. Une proteine de 26 kDa est egalement mise en evidence par immunoblot. Une sensibilisation croisee entre l'albumine de porc et de chat et les gammaglobulines de porc et de chat est confirmee par inhibition du RAST. Il s'agit d'un cas d'allergie professionnelle cutanee et respiratoire ou l'albumine et la gammaglobuline de porc se comportent comme des aeroallergenes. Nous avons mis en evidence une proteine allergisante de 26 kDa jamais decrite dans la litterature. Dans ce syndrome porc–chat, l'exposition aux allergenes de chat et l'exposition professionnelle et alimentaire a l'albumine de porc doivent etre proscrite.

Resume L'allergie IgE mediee aux proteines de lait de vache est frequente chez le nourrisson et le jeune enfant, mais peut egalement apparaitre a l'âge adulte. L'allergie aux proteines de lait de vache est souvent associee a une allergie aux laits de chevre et de brebis. L'allergie isolee aux proteines derivees de lait de brebis sans allergie associee au lait de vache semble plus exceptionnelle. Nous rapportons l'observation originale d'une patiente presentant une allergie aux proteines du lait de vache apparue a l'âge adulte, sans allergie associee aux proteines derivees du lait de brebis. Les resultats des tests cutanes, des dosages d'IgE specifiques (RAST et dot-blot) sont en faveur d'une sensibilisation a differentes proteines presentes dans les laits de vache, de chevre et de brebis, mais avec une reaction tres positive et specifique vis-a-vis des caseines d'origine bovine (α-caseine et κ-caseine).

Resume Nous avons evalue le dosage des IgE specifiques anti-rBet v 1 en tant que nouvel outil diagnostique dans la prise en charge de la pollinose printaniere. Methodes. – Cent dix-sept dossiers de patients consultant en allergologie ont ete selectionnes sur la demande d'IgE anti-rBet v 1. Les motifs de consultation etaient varies. Des dosages d'IgE anti-rBet v 2 et antipollen de bouleau (t3) etaient presents respectivement dans 82 et 28 dossiers. Le diagnostic de pollinose au bouleau etait etabli sur une histoire clinique evocatrice associee a un test cutane positif a l'extrait de pollen de bouleau. La presence d'un syndrome oral a ete recherchee chez 105 patients. L'association d'un asthme a ete consideree comme un facteur de gravite de la pollinose. Resultats. – Dans la population etudiee, la sensibilite, la specificite, la VPP et la VPN du dosage d'IgE anti-rBet v 1 sont excellentes (respectivement de 91, 82, 92 et 93 %). Dans le groupe de patients ayant eu egalement des dosages d'IgE anti-t3, la sensibilite et la specificite des IgE anti-rBet v 1 etaient superieures a celles des IgE anti-t3. Lorsque les dosages d'IgE anti-rBet v 2 etaient effectues concomitamment, ils etaient positifs dans 19,5 % des cas avec une mediane de 2,46 KU/l. Le syndrome oral etait plus frequemment associe chez les patients ayant des taux d'IgE specifiques anti-rBet v 1 superieurs a 50 KU/l. Le dosage des IgE specifiques rBet v 1 n'etait en revanche pas un element predictif de l'association d'un asthme a la pollinose. Conclusion. – Ce dosage permet de definir en partie le profil de sensibilisation des patients et de guider la desensibilisation.

We report a clinical case of a persistent left superior vena cava discovered in a 50-year-old female patient when a port-a-cath was inserted. This already seldom malformation was associated with an arteria lusoria and polysplenia with left inferior vena cava with hemiazygos continuation, right-sided stomach, short pancreas, preduodenal portal vein and intestinal malrotation, but without any cardiac abnormalities.

Resume La frequence des sensibilisations cutanees au pollen de frene commun (Fraxinus excelsior), constatee depuis quelques annees pose de nombreuses difficultes diagnostiques aux allergologues, d'autant plus que cette sensibilisation est souvent mise en evidence dans un contexte de polysensibilisations vis-a-vis de nombreux pollens. Au fur et a mesure de la progression des connaissances, la reactivite croisee avec des especes proches ou taxonomiquement eloignees est de mieux en mieux connue rendant le diagnostic de cette pollinose particulierement difficile. Dans ce travail, nous portons un interet particulier aux caracteristiques botaniques, geographiques et palynologiques du frene. Une mise au point sur la composition allergenique du pollen de frene est ensuite realisee au vu des connaissances recemment acquises.

Resume Introduction L’individualisation de la sinusite fongique allergique (SFA) est beaucoup plus recente et peut etre encore incomplete face a celle de l’aspergillose bronchopulmonaire allergique (ABPA). Leur association n’est que tres rarement rapportee dans la litterature. S’agit-il d’une association fortuite ou d’une entite nosologique fongique rhinobronchique bien documentee et/ou nouvelle ? Methodes Etude retrospective a partir d’une serie de dix SFA avec individualisation de quatre cas d’association SFA et ABPA repondant a l’ensemble des criteres diagnostiques de la litterature. Resultats L’association SFA et ABPA peut etre concomitante (2 cas) ou non (2 cas) avec parfois plusieurs annees de decalage entre l’atteinte ORL et l’atteinte bronchopulmonaire et meme apres guerison de l’atteinte initiale. Le traitement comprenant corticoides, chirurgie endoscopique (4 cas) associes aux antifongiques (2 cas) a permis la guerison (2 cas), une tres nette amelioration (1 cas) et un echec therapeutique complet pour 1 cas (recul superieur a 4 ans). Conclusion L’association, concomitante ou decalee dans le temps de la SFA et de l’ABPA, souligne l’unite des voies respiratoires hautes et basses ainsi que la parente physiopathologique entre ces deux atteintes fongiques respiratoires. La prevalence de cette association reste tres faible. Le traitement est mal standardise.

Resume Nous rapportons l’observation d’une femme de 35 ans, chez laquelle l’examen radiographique systematique a fait decouvrir un poumon gauche hyperclair, correspondant a une tumeur carcinoide stenosant presque completement la bronche souche gauche. Grâce au scanner injecte, l’hypoperfusion globale du poumon gauche est visualisee, ainsi que la tumeur. Apres une lobectomie inferieur gauche elargie, le retour a une perfusion normale est objectivee par la scintigraphie pulmonaire de perfusion, six mois plus tard. Les diagnostics differentiels du poumon clair unilateral sont discutes, ainsi que les mecanismes physiopathologiques de l’hypoperfusion et de la vasoconstriction hypoxique.

Background Ash tree, an Oleaceae member, is considered an important source of pollen allergy in Central Europe. Fra e 1 is a protein of the Ole e 1–like family, which regulates pollen tube growth. It has been suggested to be a relevant allergen from ash pollen. Objective Cloning Fra e 1-cDNA and overproducing a properly folded recombinant allergen to analyze its clinical significance. Methods Fra e 1–encoding cDNA was amplified by PCR, cloned in Escherichia coli , and sequenced. The recombinant allergen was produced in Pichia pastoris and used in immunoblotting, ELISA, histamine release, and skin prick tests. Sera and blood cells from patients sensitized to ash pollen as well as anti–Ole e 1 monoclonal and polyclonal antisera were used. Results Recombinant Fra e 1 (rFra e 1) is a glycoprotein of 145 amino acids exhibiting 82%, 88%, and 91% identity with Syr v 1, Ole e 1, and Lig v 1, allergens of the Oleaceae family. It was secreted to the extracellular medium of the yeast cultures and purified by means of 3 chromatographic steps. IgG from Ole e 1–specific antibodies recognized rFra e 1. IgE antibodies from ash-sensitized patients bound to rFra e 1 with a prevalence of 75%. The recombinant allergen induced histamine release. Twenty-nine of 30 ash-sensitized patients were positive to rFra e 1 by skin prick tests. Conclusion Fra e 1 is a relevant allergen in ash pollen sensitization. It has been efficiently produced in P pastoris and could be used in diagnosis.

The prevalence of allergic diseases has been increasing continuously and, accordingly, there is a great desire to evaluate the allergenic potential of components in our daily environment (e.g., food). Although there is almost no scientific evidence that genetically modified organisms (GMOs) exhibit increased allergenicity compared with the corresponding wild type significant concerns have been raised regarding this matter. In principle, it is possible that the allergenic potential of GMOs may be increased due to the introduction of potential foreign allergens, to potentially upregulated expression of allergenic components caused by the modification of the wild type organism or to different means of exposure. According to the current practice, the proteins to be introduced into a GMO are evaluated for their physiochemical properties, sequence homology with known allergens and occasionally regarding their allergenic activity. We discuss why these current rules and procedures cannot predict or exclude the allergenicity of a given GMO with certainty. As an alternative we suggest to improve the current evaluation by an experimental comparison of the wild-type organism with the whole GMO regarding their potential to elicit reactions in allergic individuals and to induce de novo sensitizations. We also recommend that the suggested assessment procedures be equally applied to GMOs as well as to natural cultivars in order to establish effective measures for allergy prevention.

Background Histamine-induced wheal-and-flare studies are useful, objective tests for determining differences in the peripheral H 1 -receptor blockade activities of antihistamines. Objective To evaluate the time of occurrence of 95% inhibition of histamine-induced wheal and flare after administration of fexofenadine hydrochloride, 180 mg, or cetirizine, 10 mg. Methods Forty-two volunteers (aged 18–60 years) were included in a randomized, double-blind, crossover study. Skin prick tests were undertaken using histamine (100 mg/mL) before treatment and 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4.0 hours after treatment. Wheal and flare areas were evaluated, and the time to occurrence of 95% inhibition and the frequency of subjects exhibiting 95% inhibition before median time to 95% inhibition were calculated. Results Mean ± SD time to 95% wheal inhibition was 2.46 ± 0.71 hours with fexofenadine and 2.55 ± 0.57 hours with cetirizine. The estimated mean difference between fexofenadine and cetirizine (−7 minutes in favor of fexofenadine; 2-sided 95% confidence interval, −21 to +7 minutes) was not statistically significant ( P = .34). For wheal, 29% of subjects receiving fexofenadine and 24% receiving cetirizine achieved 95% inhibition before the median time of inhibition (2.5 hours). An exact permutation test yielded a P = .37. For flare, 26% of subjects receiving fexofenadine and 10% receiving cetirizine achieved 95% inhibition before the median time of inhibition (3 hours; P = .12 by exact permutation test). Conclusions Fexofenadine and cetirizine have comparable onset of action times and similar frequencies of inhibition, as evaluated by the occurrence of 95% inhibition of histamine-induced wheal and flare.

Objectives: Sinonasal sarcoidosis remains a poorly understood and uncommon chronic granulomatous disease of unclear origin. We have attempted to characterize the main clinical and radiologic criteria for diagnosis and to discuss the treatment. Methods: A retrospective study of 15 cases of chronic, symptomatic, and biopsy-proven sinonasal sarcoidosis and a review of the literature are realized. Results: Among the 15 patients, there were 8 women and 7 men with a mean age of 44 years. The most frequent presentation was a chronic, often crusty, rarely destructive inflammatory rhinosinusitis with nodules on the septum and/or the turbinates. Pulmonary sarcoidosis was associated in 12 cases. Involvement of the nasopharynx, the pharyngolarynx, the skin, the lachrymal and salivary glands, and the liver was associated in some cases. Levels of angiotensin-converting enzyme were elevated in 10 cases and normal in 3 cases. Gallium scan performed in three cases was positive. Radiologic studies showed nodules on the septum and/or the turbinates in 14 cases, complete or subtotal opacification of the sinuses and/or the nasal cavities in 13 cases, and nasopharyngeal or pharyngolaryngeal lesions in 4 cases. Treatment with corticosteroids, methotrexate, azathioprine, and surgery appear globally disappointing in view of the side effects and the relapses during a long follow-up (3–15 yr; mean, 6 yr). Conclusion: On the basis of this study, we propose the following diagnostic criteria: 1) histopathologic confirmation of noncaseating granuloma; 2) chronic rhinosinusitis poorly responsive to conventional treatment and radiologic evidence of rhinosinusitis, often with nodules on the septum and/or the turbinates; 3) elevated level of angiotensin-converting enzyme; 4) positive gallium scan (if performed); 5) frequent evidence of systemic, especially pulmonary, sarcoidosis; 6) no evidence of other granulomatous diseases, such as Wegener granulomatosis.

Resume Introduction Le pharmacien joue un role essentiel dans la prise en charge du patient asthmatique du fait de la frequence de ses visites en officine pour la delivrance de ses medicaments. Methodes Afin d’evaluer le comportement et les connaissances des pharmaciens du Bas-Rhin dans l’asthme, 120 pharmaciens ont ete selectionnes au hasard pour repondre a un questionnaire standardise. Resultats Les 86 pharmaciens ayant participe a l’etude ont une bonne connaissance generale de l’asthme et de son traitement. Cependant, 26,4 % des pharmaciens connaissaient l’ensemble des criteres de gravite d’une crise d’asthme. Parmi les 57 pharmaciens ayant effectue une demonstration de l’utilisation de dispositifs inhales, 16,3 % ont realise toutes les etapes de manipulation d’un spray-doseur. Ces resultats sont comparables a ceux des medecins non pneumologues et des infirmieres pour lesquels la mauvaise utilisation varie de 63 a 100 % et 65 a 96 %, respectivement. Les scores moyens des pharmaciens etaient de 10,5/12 etapes (± 1,2) pour l’aerosol-doseur, 10,4/11 (± 1,0) pour le Turbuhaler ® , 9,3/12 (± 1,7) pour l’Autohaler ® et 8,1/9 (± 0,9) pour la chambre d’inhalation. L’attente principale du patient asthmatique vis-a-vis du pharmacien concerne la methode d’utilisation des dispositifs prescrits (87,2 %), soulignant ainsi le manque d’informations recues ou retenues par le patient lors de la prescription. Conclusion L’amelioration des connaissances en matiere de signes de gravite de l’asthme et d’utilisation des dispositifs inhales pourrait etre utilement l’un des objectifs de formation du pharmacien d’officine.