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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.

Allergen-specific immunotherapy (SIT) offers a disease specific causative treatment by modifying the allergen-specific immune response allowing tolerance to higher doses of allergen and preventing progression of allergic diseases. It may be considered in patients allergic to furry animals. Current mammalian allergy vaccines are still prepared from relatively poorly defined allergen extracts and may induce immediate and late phase side effects. Although the mechanisms of SIT are still not fully understood, the more recent approaches report different strategies to reduce both allergen-specific IgE as well as T cell reactivity. The availability of recombinant allergens and synthetic peptides from the mammalian species has contributed to formulating new allergy vaccines to improve SIT for furry animal allergy. The majority of studies have focused on the major cat allergen Fel d 1 due to its extensive characterization in terms of IgE and T cell epitopes and to its dominant role in cat allergy. Here we review the most recent approaches, e.g., synthetic peptides, recombinant allergen derivatives, different hypoallergenic molecules, and recombinant allergens coupled to virus-like particles or immunomodulatory substances as well as strategies targeting the allergen to Fcγ receptors and the MHC class II pathway using a new route for administration. Many of the new vaccines hold promise but only a few of them have been investigated in clinical trials which will be the gold standard for evaluation of safety and efficacy in allergic patients.

The house dust mite (HDM) Dermatophagoides pteronyssinus is one of most important allergen sources and a major elicitor of allergic asthma. We screened a D. pteronyssinus expression cDNA library with IgE Abs from HDM allergic patients. A cDNA coding for a new major allergen was isolated, which showed sequence homology to peritrophins, which contain chitin-binding domains and are part of the peritrophic matrix lining the gut of arthropods. The mature Der p 23 allergen was expressed in Escherichia coli as an 8-kDa protein without its hydrophobic leader sequence and purified to homogeneity. It reacted with IgE Abs from 74% of D. pteronyssinus allergic patients (n = 347) at levels comparable to the two major HDM allergens, Der p 1 and Der p 2. Thus, Der p 23 represents a new major D. pteronyssinus allergen. Furthermore, rDer p 23 exhibited high allergenic activity as demonstrated by upregulation of CD203c expression on basophils from D. pteronyssinus allergic patients. Immunogold electron microscopy localized the allergen in the peritrophic matrix lining the midgut of D. pteronyssinus as well as on the surface of the fecal pellets. Thus, we identified a new major D. pteronyssinus allergen as peritrophin-like protein. The high allergenic activity of Der p 23 and its frequent recognition as respiratory allergen may be explained by the fact that it becomes airborne and respirable through its association with mite feces. Der p 23 may be an essential component for diagnosis and specific immunotherapy of HDM allergy.

International audience; BACKGROUND: Fine particulate matter has been linked to allergies by experimental and epidemiological data having used aggregated data or concentrations provided by fixed-site monitoring stations, which may have led to misclassification of individual exposure to air pollution. METHODS: A semi-individual design was employed to relate individual data on asthma and allergy of 5338 school children (10.4 +/- 0.7 years) attending 108 randomly chosen schools in 6 French cities to the concentrations of PM2.5 (fine particles with aerodynamic diameter 2.5 microm) assessed in proximity of their homes. Children underwent a medical visit including skin prick test (SPT) to common allergens, exercise-induced bronchial (EIB) reactivity and skin examination for flexural dermatitis. Their parents filled in a standardised health questionnaire. RESULTS: After adjustment for confounders and NO2 as a potential modifier, the odds of suffering from EIB and flexural dermatitis at the period of the survey, past year atopic asthma and SPT positivity to indoor allergens were significantly increased in residential settings with PM2.5 concentrations exceeding 10 microg/m3 (WHO air quality limit values). The relationships were strengthened in long-term residents (current address for at least 8 years). CONCLUSIONS: Findings support the hypothesis that changes in allergy prevalence observed in recent decades might be partly related to interactions between traffic-related air pollution and allergens. Further longitudinal investigations are needed to corroborate such results.

Program and Abstracts of Papers to be Presented During Scientific Sessions - AAAAI Annual Meeting 2006

IgE-mediated allergy affects >25% of the population in industrialized countries. Repeated contact with the disease-eliciting allergens induces rises of allergen-specific IgE Abs and progression of the disease to more severe manifestations. Our study uses a type of vaccine that is based on genetically modified allergen derivatives to treat allergic patients. We developed hypoallergenic derivatives of the major birch pollen allergen, Bet v 1, by genetic engineering and vaccinated birch pollen-allergic patients ( n = 124) in a double-blind, placebo-controlled study. Active treatment induced protective IgG Abs that inhibited allergen-induced release of inflammatory mediators. We also observed a reduction of cutaneous sensitivity as well as an improvement of symptoms in actively treated patients. Most important, rises of allergen-specific IgE induced by seasonal birch pollen exposure were significantly reduced in vaccinated patients. Vaccination with genetically engineered allergen derivatives is a therapy for allergy that not only ameliorates allergic reactions but also reduces the IgE production underlying the disease.

International audience; BACKGROUND: Whereas effects on allergic and respiratory health have been established for passive tobacco smoking, contradictory results still exist for active tobacco smoking. OBJECTIVE: Whether adolescents with asthma and allied diseases have higher rates of active smoking compared with adolescents without asthma was assessed after controlling for environmental tobacco smoking exposure. METHODS: A population-based sample of 14,578 adolescents was enrolled in an epidemiological survey on allergies in France. RESULTS: After controlling for age, sex, geographic region, familial allergy and passive smoking, current (in the past year) wheezing (12.4%), current asthma (5.6%), lifetime asthma (12.3%), current rhinoconjunctivitis (13.9%), lifetime hayfever (14.4%) and current eczema (9.3%) but not lifetime eczema (22.5%) were all significantly related to active smoking (>1 cigarette/day) (9.3%). A higher risk of current wheezing, current and lifetime asthma or current eczema was seen in smokers exposed to passive smoking compared with smokers not exposed to it using a polychotomous logistic regression model, in which the different modalities of exposure to active and passive smoking constituted the response variable. Passive smoking was significantly associated only with current diseases. Active smoking was also highly related to both severe asthma (OR=4.02; 95% confidence interval: 1.37, 11.79) and severe rhinoconjunctivitis (OR=2.95; 1.58, 5.49). The highest rate of adolescents suffering from the co-morbidity of lifetime asthma and hayfever (3.6%) was also seen in active smokers compared with passive and non-smokers (5.5% vs. 3.6% and 3.1%, respectively; P=0.001). CONCLUSIONS: Being asthmatic or allergic does not seem to act as a deterrent towards starting active smoking or continuing to smoke in adolescence. Results suggest the need for considering individual allergic status in programming health educational activities aimed at reducing smoking among adolescents.

Aims: To estimate the general and specific incidence of occupational asthma in France in 1996–99; and to describe the distribution of cases by age, sex, suspected causal agents, and occupation. Methods: New cases of occupational asthma were collected by a national surveillance programme, based on voluntary reporting, named Observatoire National des Asthmes Professionnels (ONAP), involving a network of occupational and chest physicians. For each case, the reporting form included information on age, sex, location of workplace, occupation, suspected causal agent, and methods of diagnosis. Estimates of the working population, used to calculate incidence rates by age, sex, region, and occupation, were obtained from the Institut National de la Statistique et des Etudes Economiques (INSEE) and from the French Securite Sociale statistics. Results: In 1996–99, 2178 cases of occupational asthma were reported to the ONAP, giving a mean annual rate of 24/million. Rates in men were higher than rates in women (27/million versus 19/million). The highest rate was observed in the 15–29 years age group (30/million). The most frequently incriminated agents were flour (20.3%), isocyanates (14.1%), latex (7.2%), aldehyde (5.9%), persulphate salts (5.8%), and wood dusts (3.7%). The highest risks of occupational asthma were found in bakers and pastry makers (683/million), car painters (326/million), hairdressers (308/million), and wood workers (218/million). Conclusion: Despite likely underreporting, the number of cases of occupational asthma reported to the ONAP was approximately twice the number of compensated cases over the same period. The relevance of the programme is confirmed by the reproducibility of the results year after year, and its consistency with other surveillance programmes. The ONAP programme is useful for the identification of targets for primary prevention.

Increased non-specific bronchial hyperresponsiveness (BHR) has been reported after positive reaction to isocyanates in patients with isocyanate-sensitive asthma. The increased responsiveness may, however, also precede the asthma attack. We therefore compared non-specific BHR to a cholinergic agent before and after exposure to toluenediisocyanate (TDI) that induced no asthma symptoms in 11 workers with isocyanate-related asthma. Patients were exposed for 3 consecutive days to progressively increasing doses of TDI (5, 10, and 20 ppb min −1 for 20 min) in an exposure chamber with continuous TDI monitoring. No immediate nor late asthmatic bronchial reaction was observed in any patient after any dose of TDI during or after challenge. A significant increase in non-specific BHR was noted 24 h after the last dose of TDI challenge, however. This increase was at least one doubling dose for seven of 11 patients. In conclusion, our study shows that, in patients with isocyanate-induced asthma, exposure to TDI induces a slight but significant increase in non-specific BHR in the absence of any immediate or late bronchial response to isocyanate. This result, which requires further confirmation, may justify a proposal to measure non-specific BHR, even after a negative specific inhalation test to TDI, as an additional diagnostic element for TDI-induced occupational asthma, to help lower the percentage of the undetected occupational asthma cases.

The appearance of wheezes and changes in inspiratory breath (vesicular) sound intensity (BSI) were monitored in patients undergoing routine methacholine challenge test (MCT). The results were compared with changes in spirometry and to airway hyper-responsiveness (AH). Fifty-four patients were examined. Spirometry was performed before and after the inhalation of cumulative doses of methacholine starting from 25 μg; a fall in forced expiratory volume in 1 s (FEV 1 ) by 20% or more was considered as significant. Lung auscultation was performed by two observers simultaneously using a special stethoscope placed sequentially over the posterior right and left upper (interscapular region, 5 cm from the fourth thoracic vertebra) and lower lung zones (5 cm below the scapulae). Symptoms were recorded by the patients on a visual analogue scale. In 27 patients, the MCT was positive (MCT+) and in 27 patients it was negative (MCT −). Wheezes were identified at PD 20 in 12 MCT + patients while reduced BSI alone was found in 11 patients; in four patients, auscultation was normal. In 20 MCT + patients, either wheezes, diminished BSI or both were heard, one to several steps before reaching PD 20 . In the MCT − group, wheezes were detected in two patients and diminished BSI in four. In MCT + patients, the mean (± sd) perception of symptoms at end-challenge was 33% (± 26), whereas in MCT − patients, it was 13·6% (± 22). Complete interobserver agreement was found in 95·7% of ausculations performed (Kappa coefficient=0·846). Coupled to spirometry, lung auscultation may prove useful in airway challenge testing provided the concept is accepted that wheeze appearance and, by extension, an acute decrease in BSI, is as legitimate a manifestation of AH as a fall in FEV 1 .

House dust mites (HDMs) belong to the most potent indoor allergen sources worldwide and are associated with allergic manifestations in the respiratory tract and the skin. Here we studied the importance of the high-molecular-weight group 11 allergen from Dermatophagoides pteronyssinus (Der p 11) in HDM allergy. Sequence analysis showed that Der p 11 has high homology to paramyosins from mites, ticks, and other invertebrates. A synthetic gene coding for Der p 11 was expressed in Escherichia coli and rDer p 11 purified to homogeneity as folded, alpha-helical protein as determined by circular dichroism spectroscopy. Using antibodies raised against rDer p 11 and immunogold electron microscopy, the allergen was localized in the muscle beneath the skin of mite bodies but not in feces. IgE reactivity of rDer p 11 was tested with sera from HDM-allergic patients from Europe and Africa in radioallergosorbent test–based dot-blot assays. Interestingly, we found that Der p 11 is a major allergen for patients suffering from atopic dermatitis (AD), whereas it is only a minor allergen for patients suffering from respiratory forms of HDM allergy. Thus, rDer p 11 might be a useful serological marker allergen for the identification of a subgroup of HDM-allergic patients suffering from HDM-associated AD.

The present case report describes a case of invasive pulmonary aspergillosis with cerebromeningeal invasion in an asthmatic non-immunocompromised patient. This fatal complication occurred despite early anti-fungal antibiotherapy after a 2-week course of intravenous corticosteroid therapy for treatment of an exacerbated asthma. Diagnostic and therapeutic procedures are discussed.

1 Cyclic adenosine 3',5'-monophosphate (cyclic AMP)- and cyclic guanosine 3',5'-monophosphate (cyclic GMP)-phosphodiesterase activities from rat lung were selectively inhibited by ZK 62711 and M & B 22948, respectively. Theophylline and papaverine inhibited both activities. 2 Rat lung strips contracted by carbachol were relaxed by 4-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyrrolidone (ZK 26711, EC25 = 7 x 10(-8)M) and 2-O-propoxyphenyl-8-azapurin-6-one (M & B 22948, EC25 = 5 x 10(-7)M) indicating relaxant properties of both cyclic AMP and cyclic GMP. 3 The antigen-induced histamine release from human basophils was inhibited by ZK 62711 (IC25 = 8 x 10(-7)M), whereas M & B 22948 had no effect. On the contrary, the release from rat mast cells was inhibited by M & B 22948 (IC25 = 10(-6)M), while ZK 62711 had no effect. 4 These data show an inhibitory effect of cyclic AMP on histamine release to be involved with basophils, whereas cyclic GMP is predominantly involved with mast cells. Is is suggested that the antianaphylactic properties of cyclic nucleotide phosphodiesterase inhibitors are mainly linked to the increase of cyclic GMP.